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PubMed1979

Methodological issues in tardive dyskinesia research.

Research into tardive dyskinesia, an involuntary movement disorder secondary to chronic neuroleptic treatment, has so far produced conflicting results with no clear clinical applications. Heterogeneous diagnostic criteria, research designs, and rating scales, plus an emphasis on single-drug trials, are probably responsible. A strategy of developing pharmacological response profiles for patients participating in tardive dyskinesia research is suggested as one way to produce meaningful data, which may delineate pharmacological and clinical subtypes that would respond to different treatment approaches. Further suggestions are made about future trends in this area of research.

Clinical Trials as Topic↗
PubMed1978

Studies of process--outcome correlations in medical care evaluations: a critique.

The validity of process evaluations of medical care has been challenged by a number of studies which purport to show that process and outcome measures are unrelated. However, each of the studies had numerous methodological flaws which biased their results against finding a relationship: either their outcome measures had questionable validity, their research designs were inappropriate, or the statistical analyses were poorly conceived. Better studies have found significant, although modest, correlations between process and outcome measures. Since the validity of outcome measures has never been determined, there is little reason at present for believing that outcome measures are more valid than process measures.

Evaluation Studies as Topic↗
PubMed1978

Therapeutic antagonism between anticholinergics and neuroleptics: possible involvement of cholinergic mechanisms in schizophrenia.

We have answered technical criticisms of our work in which anticholinergic agents were added to ongoing neuroleptic treatment in an ABA' research design. The suggested analysis of variance for repeated measures of the three periods is inappropriate because of the expected carryover effects from continuous neuroleptic treatment. The multivariate analysis of various parameters seems unsuitable because homogeneity of covariance cannot be ensured due to the heterogeneity of schizophrenia and the diverse factors represented in the psychopathology measures. We have summarized the results of recent parametric and nonparametric analyses of combined data from our three studies to show that the significant effects clearly pointed to therapeutic antagonism between anticholinergic agents and neuroleptics. We suggest that cholinergic neurons may be part of some crucial discriminative control mechanisms in the brain organization that are ineffective in schizophrenia and lead to a relative overactivity of the opposing catecholaminergic neurons in the midbrain-limbic circuitry which promote repetition of behaviors in goal-directed activity.

Antipsychotic Agents↗
PubMed1979

Multiple-baseline design in instructional research: pitfalls of measurement and procedural advantages.

The multiple-baseline design has utility for evaluating the instructional programs used with mentally retarded persons; however, there are several pitfalls of measurement that may be encountered in using this design. Subjects' performance may be inadvertently altered by (a) repeated testing during baseline, (b) a procedural contrast between training and testing, and (c) inaccurate generalization during testing. Procedures to mitigate the effects of these problems were recommended. The pitfalls may arise in part because of the direct interpersonal nature of measuring the dependent variable in instructional research. Also, the pitfalls are not inherent in the multiple-baseline design per se but are issues of measurement that may occur in other designs as well. Finally, the advantage of using the multiple-baseline design to study covariation of responding was highlighted.

Adolescent↗
PubMed1979

HZI systems for EEG parametrization and classification of psychotropic drugs.

The EEG effects of twenty, clinically most frequently used psychotropic drugs and five placebos were studied in 75 male volunteers in five simultaneously designed basic studies. In each of the five studies single oral dosages of five drugs (well known representatives of neuroleptics, antidepressants, anxiolytics and psychostimulants, as well as placebos) were investigated in 15 subjects in a double-blind latin-square research design using the methods of the Quantitative Pharmaco-EEG. The results demonstrated that the therapeutically equivalent effective compounds also have similar effects on human EEG. With a classification rule, based on discriminant function 20, and with a classification rule, based on correlation statistics 19 of 25 compounds could be reclassified into correct clinical-therapeutic psychotropic drug groups. It is suggested that CEEG is an important tool in predicting and describing psychotropic properties of compounds, and should routinely be used in psychotropic drug development.

Adult↗
PubMed2026

From fear to empowerment: the impact of employees AI awareness on workplace well-being - a new insight from the JD-R model.

PURPOSE: The primary purpose of the study was to explore the impact of health workers' awareness of artificial intelligence (AI) on their workplace well-being, addressing a critical gap in the literature. By examining this relationship through the lens of the Job demands-resources (JD-R) model, the study aimed to provide insights into how health workers' perceptions of AI integration in their jobs and careers could influence their informal learning behaviour and, consequently, their overall well-being in the workplace. The study's findings could inform strategies for supporting healthcare workers during technological transformations. DESIGN/METHODOLOGY/APPROACH: The study employed a quantitative research design using a survey methodology to collect data from 420 health workers across 10 hospitals in Ghana that have adopted AI technologies. The study was analysed using OLS and structural equation modelling. FINDINGS: The study findings revealed that health workers' AI awareness positively impacts their informal learning behaviour at the workplace. Again, informal learning behaviour positively impacts health workers' workplace well-being. Moreover, informal learning behaviour mediates the relationship between health workers' AI awareness and workplace wellbeing. Furthermore, employee learning orientation was found to strengthen the effect of AI awareness on informal learning behaviour. RESEARCH LIMITATIONS/IMPLICATIONS: While the study provides valuable insights, it is important to acknowledge its limitations. The study was conducted in a specific context (Ghanaian hospitals adopting AI), which may limit the generalizability of the findings to other healthcare settings or industries. Self-reported data from the questionnaires may be subject to response biases, and the study did not account for potential confounding factors that could influence the relationships between the variables. PRACTICAL IMPLICATIONS: The study offers practical implications for healthcare organizations navigating the digital transformation era. By understanding the positive impact of health workers' AI awareness on their informal learning behaviour and well-being, organizations can prioritize initiatives that foster a learning-oriented culture and provide opportunities for informal learning. This could include implementing mentorship programs, encouraging knowledge-sharing among employees and offering training and development resources to help workers adapt to AI-driven changes. Additionally, the findings highlight the importance of promoting employee learning orientation, which can enhance the effectiveness of such initiatives. ORIGINALITY/VALUE: The study contributes to the existing literature by addressing a relatively unexplored area - the impact of AI awareness on healthcare workers' well-being. While previous research has focused on the potential job displacement effects of AI, this study takes a unique perspective by examining how health workers' perceptions of AI integration can shape their informal learning behaviour and, subsequently, their workplace well-being. By drawing on the JD-R model and incorporating employee learning orientation as a moderator, the study offers a novel theoretical framework for understanding the implications of AI adoption in healthcare organizations.

Humans↗
PubMed1979

Effectiveness of psychotherapeutic counseling in methadone maintenance.

Therapeutic counseling has been widely adovacted with methadone maintenance, but its effectiveness has not been demonstrated. A review of the literature revealed a dearth of scientific investigations comparing treatment outcomes with and without counseling services. The few studies which have been reported seem to suggest that counseling does not significantly change treatment outcomes as measured by the usual indicators of illicit drug use, arrests, employment, and retention in the program. These studies suffered from a number of methodological flaws, however, including failure to adhere to research design, small sample size, poorly matched control groups, inadequate outcome criteria, and absence of post-treatment follow-up. Previous investigators have been nearly unanimous in calling for further studies of this issue. Since the cost of counseling services represents a major portion of treatment program budgets, there is an urgent need to document the effectiveness of these services with definitive studies.

Counseling↗
PubMed2026

Evaluating a coaching intervention for Dementia Care Practice Recommendations in care communities: a cluster randomized controlled trial.

BACKGROUND AND OBJECTIVES: Within care communities, including nursing home and assisted living settings, person-centered dementia care, outlined by the 2018 Alzheimer's Association Dementia Care Practice Recommendations (DCPR), is foundational to quality care and improving staff outcomes. This study evaluates the effectiveness of a 6-month Care Community Coaching Program in enhancing person-centered dementia care and staff outcomes in alignment with the DCPR. RESEARCH DESIGN AND METHODS: A cluster randomized controlled trial was conducted with 77 care communities and 434 staff members-227 from 38 intervention communities and 207 from 39 control communities. Outcomes included employee satisfaction (areas: job satisfaction, team building and communication, scheduling and staffing, training, and management and leadership), person-centered care practices (areas: workplace practices, individualized care and services, caregiver-resident relationships), and dementia care confidence, measured pre- and post-intervention and at 3-month follow-up. A generalized Estimating Equations model was used to estimate intervention effects. RESULTS: Care communities assigned to the coaching intervention showed statistically significant improvements in employee satisfaction and staff perceptions of workplace practices and individualized care. No statistically significant effects on staff perceptions of caregiver-resident relationships or on dementia care confidence were noted. DISCUSSION AND IMPLICATIONS: Findings provide direction for future research and intervention development, including examining coaching's impact on resident quality outcomes, and incorporating skills training into future models. Collectively, findings provide evidence of the effectiveness of a Care Community Coaching Program in improving staff outcomes and person-centered practices, offering a practical path towards improving the lived experience of residents and staff in care communities.

Humans↗
PubMed2026

Changes of DNA methylation and gene expression profile in placental villi and chorioamniotic membranes under preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication with elusive pathogenesis. Although epigenetic dysregulation is implicated, its layer-specific placental roles are poorly defined. This study aimed to identify shared and layer-specific epigenetic alterations in PE by profiling DNA methylation and gene expression in placental villi (PV) and chorioamniotic membranes (CAM). RESEARCH DESIGN AND METHODS: PV and CAM samples were collected from 7 normal and 8 PE pregnancies, and three public DNA methylation datasets (GSE98224, GSE44667, GSE75196) were integrated. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified based on whole-genome methylation and transcriptome sequencing. Layer-specific and shared gene sets were identified by cross-analysis, with functional annotation using Gene Ontology (GO). RESULTS: EM-seq revealed a hypermethylation-dominant, tissue-specific methylation landscape in PE placentas. Cross-tissue comparison identified shared DMGs between the two layers, including nine key genes consistently altered in public datasets. Integrated analysis in PV further identified 22 co-dysregulated genes, enriched in thermoregulation, maternal-fetal immunity, signal transduction, and cell differentiation. CONCLUSIONS: This study elucidates the shared and layer-specific dysregulation of gene networks at methylomic and transcriptomic levels in PE placenta. Comparing PV and CAM highlights placental epigenetic heterogeneity and dysfunction, offering novel clues for mechanistic research and layer-targeted therapies.

Humans↗
PubMed1979

Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating.

This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.

Animals↗
PubMed2024

Mendelian randomization study on the causal effect of herpes simplex virus infection on idiopathic pulmonary fibrosis.

BACKGROUND: Previous observational studies have shown that past infection of herpes simplex virus (HSV) is associated with idiopathic pulmonary fibrosis (IPF). The present study aims to identify the causal link between HSV infection (exposure factor) and IPF (outcome factor). RESEARCH DESIGN AND METHODS: To date, the largest publicly available genome-wide association study (GWAS) for HSV infection (1,595 cases and 211,856 controls from Finnish ancestry) and for IPF (1,028 cases and 196,986 controls from Finnish ancestry) were used to perform this two-sample Mendelian randomization (MR) study. RESULTS: We found no significant pleiotropy or heterogeneity of all selected nine HSV infection-associated genetic instrumental variants (IVs) in IPF GWAS dataset. Interestingly, we found that as HSV infection genetically increased, IPF risk increased based on an inverse-variance weighted (IVW) analysis (odds ratio [OR] = 1.280, 95% confidence interval [CI]: 1.048-1.563; p = 0.015) and weighted median (OR = 1.321, 95% CI: 1.032-1.692; p = 0.027). CONCLUSIONS: Our analysis suggests a causal effect of genetically increased HSV infection on IPF risk. Thus, HSV infection may be a potential risk factor for IPF.

Humans↗
PubMed2026

Circadian-rhythm-based dynamics of the secretome in molecular subtypes of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) lacks a reliable diagnostic biomarker, largely due to its asymptomatic onset and frequent late-stage detection, resulting in a poor 5-year survival rate. Identifying biomarkers for timely diagnosis is critical. Cancer cells display distinct protein regulation changes that drive disease hallmarks, and characterizing these across PDAC subtypes may provide insights into disease progression. RESEARCH DESIGN AND METHODS: In this study, a label-free quantitative (LFQ) proteomics approach using mass spectrometry (MS) was employed to profile circadian rhythm-regulated proteins in the secretome of PDAC cell lines. RESULTS: LFQ analysis revealed rhythmic protein regulation patterns, reflecting temporal control of biological processes in PDAC. Upregulated pathways included signal transduction, glycolysis, angiogenesis, and protein synthesis, indicating enhanced metabolic and proliferative activity. Downregulated immune pathways suggested potential immune modulation. Comparative analysis revealed subtype-specific patterns: the quasi-mesenchymal subtype exhibited higher levels of metabolic and extracellular matrix (ECM) remodeling proteins, while the classical subtype showed higher levels of ECM-degrading proteins, consistent with known phenotypic differences. CONCLUSION: These findings highlight rhythmically regulated proteins as potential subtype-specific markers in PDAC and provide a basis for future validation studies. Mass spectrometry proteomics data are available via the ProteomeXchange Consortium (PRIDE: PXD054693).

Humans↗
PubMed1979

The assessment and meaning of intraobserver error in population studies based on discontinuous cranial traits.

Intraobserver scoring precision of 50 discontinuous (discrete) cranial traits was assessed on a sample of 125 intact Iroquois crania using the square of the phi coefficient. Scoring consistency was high for most traits although several were subject to low precision (phi 2 less than 0.7). Most errors were random rather than systematic. Taken collectively the problematic traits exceeded their expected contribution to MMD coefficients among four Woodland samples from southern Ontario. A traitlist with the problematic variants excluded produced more meaningful biological relationships among the samples. Further, the % contribution of the problematic traits increased with the time interval between the scoring of the individual samples. It was suggested that intraobserver error could effectively distort the interpretation of biological relationships and that it must in part be responsible for the poor performance reported for discontinuous traits in some studies. Therefore, it was argued that the results support rather than compromise the use of discontinuous skeletal traits in population studies and that the assessment of intraobserver error should be a standard procedure of the research design.

Canada↗
PubMed1979

Judgments of trained observers on adverse drug reactions.

Patients (672) admitted to a department of medicine during five consecutive months were followed by an investigator who identified 110 clinical manifestations which could have been considered adverse drug reactions. From these, 42 were excluded because they did not correspond to the definition of adverse reaction or they were inadequately documented. The remaining 68 cases were submitted to three independent observers who had to reply to a series of questions; from these replies five degrees of probability for the reaction itself were deduced. Reactions (54; 49% of the manifestations reported) were considered as certain or probable by at least two observers, but only 27 rections of these (25%) were attributed to the same drug by all three observers. There was a low level of agreement between any two observers (paired agreement ratio: 0.6 to 0.7) and little difference of agreement between any one observer and each of the others (personal agreement ratio: 0.6 to 0.7).

Drug-Related Side Effects and Adverse Reactions↗
PubMed1979

Problems of university-based scientists associated with clinical trials.

University faculty members who participate in clinical trials face a number of difficulties in connection with this association. Publication opportunities are often limited, and individual scholarship is difficult to express and evaluate within the context of a cooperative trial. Merit increases, promotion, and the award of tenure will usually require evidence of scholarly achievement outside the trial setting. For this reason, it seems inadvisable to recommend that a young investigator devote a major portion of his scholarly and research time to such an activity. A possible exception may be a full-time appointment for 1 to 2 years. Nonetheless, cooperative clinical trials are an important investigative tool and they should continue to be associated with academic centers. If appropriate administrative arrangements can be made, it should be possible to solve the academic problems of the young investigator associated with such trials.

Clinical Trials as Topic↗
PubMed1979

Effective clinical trials investigators and adequate incentives.

Because of the importance of randomized controlled trials in medical research and development, the most competent and qualified individuals from a variety of medical specialties are needed as investigators for these trials. Such people must be highly dedicated to the improvement of human health and they must also be cooperative and able to work in the highly disciplined atmosphere that such a trial demands. In order that the trial investigators be persons of high caliber, certain incentives must be guaranteed, such as recognition of one's contributions to the trial itself, publications, and opportunities to present study results at various meetings. University and medical school policies on promotion and tenure need to be reassessed bearing in mind the complexity of achieving optimal recognition of the individuals investigator's contributions to a clinical trial.

Clinical Trials as Topic↗
PubMed1978

Premorbid psychological factors as related to cancer incidence.

In planning for studies relating psychological factors and/or stress (PF&/oS) to cancer, one should be aware of epidemiological findings that might contribute to or even account wholly for any found relationships. Most studies have not examined the known biological causes of cancer, nor have they described a rationale for relationships sought. The two broad mechanisms leading to cancer, carcinogens and lowered resistance to it, include physical and chemical causes, viruses and chronic infection, medication, genetic predisposition, hormonal stimuli, and aging. Interfering variables may bias or dilute a real relationship. Validity and reliability of instruments measuring PF&/oS are so variable as to warrant considerable care in their use. The latent periods of different cancers are measured in years, not months, with consequent potent impact on possible inferences drawn from prebiopsy and short prospective studies. In these and in retrospective studies, cancer can have strong and biasing effects on apparently straightforward PF&/oS measurements, as can iatrogenic effects. Some theoretical issues are discussed. The known prospective studies are discussed and reasons are given for the view that they are less convincing then many seem to think. A sketch of a model relating PF&/oS to cancer appearance is outlined, with some theoretical implications, and issues in research design are addressed.

Animals↗