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Interrater reliability of the Structured Clinical Interview for the Positive and Negative Syndrome Scale for schizophrenia.

The Swedish version of the Positive and Negative Syndrome Scale for schizophrenia (PANSS) has been tested and construct validity, internal reliability and interrater reliability have been demonstrated to be quite satisfactory. However, the interrater reliability of the negative symptoms was unsatisfactory low. In this study, the Swedish version of the Structured Clinical Interview for the PANSS has been tested. The interrater reliability is increased as compared with the inter-rater reliability achieved by means of the PANSS. As concerns the positive scale, the intraclass coefficients increased to 0.98-0.99 with the SCID-PANSS. For the negative scale, the intraclass coefficients increased to 0.83-0.90 with the SCID-PANSS, and for the general scale the increase was to 0.95-0.98 with the SCID-PANSS. It was also demonstrated that the interrater reliability is higher for the positive and the negative factors derived from the PANSS than for the positive and the negative scales.

Anxiety Disorders↗

Long-term effects of transference interpretations: comparing results from a quasi-experimental and a naturalistic long-term follow-up study of brief dynamic psychotherapy.

A follow-up study, using a quasi-experimental non-equivalent groups comparison design, the so-called regression discontinuity design, reported a negative long-term effect of a high frequency of transference interpretations given to patients in brief dynamic psychotherapy who had been deemed highly suitable for such treatment. The major threat to internal validity of the findings was the possibility that the patients who were evaluated as highly suitable for dynamic psychotherapy might be the ones with the naturally worst outcomes, independent of therapy technique (selection maturation). Data from a similar naturalistic study with no quasi-experimental manipulation of the treatment technique revealed, however, that highly suitable and relatively less suitable patients had similar outcomes. This makes selection maturation a less plausible confound of the (negative) treatment effect estimated in the quasiexperimental study. A high frequency of transference interpretations in brief dynamic psychotherapy seems to be causally related to less favourable long-term dynamic change.

Adaptation, Psychological↗

Providing care in an infectious disease clinic. Why students volunteer.

This qualitative study explores the motivations of dental students who volunteered as care providers for patients identified as carriers of infectious diseases. The study involved 12 students, seven 4th year and five 3rd year students who worked 1-2.5 days per week in an infectious disease clinic in a dental school in the northeastern United States. 4 faculty members who also volunteered their time in the clinic supervised the students. Personal interviews were conducted with each student to determine their reasons for volunteering and to explore the perceived significance of their experiences in the clinic. Internal validity was established through group interviews wherein responses during the personal interviews were discussed with the students. All 12 students were interested in Oral Medicine and all 4th year students had completed a course on HIV-AIDS for their selective requirement. Students expressed willingness to care for patients who are medically compromised in anticipation of an increase of this type of patients in their future practice. Previous exposure to a family member or friend or patients (non-dental) who were terminally ill or to patients with HIV was another common reason. All 12 students preferred to work in the infectious disease clinic more than in other school clinics. They felt that there was more faculty-student interaction and a more stimulating learning atmosphere that the faculty created. The students felt that the patients treated in the clinic were more appreciative. Students also claim they experienced more team spirit among their fellow students and staff and that the clinic atmosphere was more relaxed and less competitive. Students got the most satisfaction from helping patients who were perceived to have had problems in accessing care prior to their visit to the clinic. Results of the study show that the students volunteered to treat patients who are known to have infectious diseases such as HIV/AIDS because they find personal and academic satisfaction from working in a clinic which provides care to individuals with specific medical needs.

Attitude of Health Personnel↗

Encoding of the subjective intensity of sharp dental pain.

This paper is a review and a discussion of our own pain research over the last decade. It is of a methodological and theoretical character and deals with preparation technique, choice of electrodes, control experiments involving pulpotomy and reliability tests of psychophysical methods for pain measurements, and the neuronal population encoding of sharp dental pain. The electrophysiological recording technique selectively picks up electrical activity induced in pulpal A-delta nerve fibers. The sensation of pain was quantified by means of an intermodal matching technique, finger span (PAS), in combination with sensory verbal descriptors covering a range from very, very weak to maximal pain. When a cold stimulus, ethyl chloride, was applied on the tooth surface a close agreement was demonstrated between intradental A-delta nerve activity (INA) and the sensation magnitude of pain (PAS) with respect to curve amplitude and time course. The high covariation of the neural and perceptual response measures indicated a good internal validity and confirmed also the basic soundness and the applicability of the procedures employed. For the purpose of further analyzing the functional relation of INA to PAS we studied specifically the effect of cold stimuli of different intensity on the integrated nerve response. Only sharp, shooting pain was accepted as a sensorial, perceptual correlate of the intradental A-delta nerve activity. Since an increase in amplitude was generally accompanied by an increase in duration of the responses, the fundamental question was raised how to best describe and characterize the neural and perceptual responses so that they most adequately reflect the information processing of the intensive aspect of sharp dental pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cerebral blood flow in preterm infants during the first week of life.

Forty-two preterm infants of 28-33 weeks of gestation were studied once during the first week of life by 133-Xenon clearance after intravenous injection to estimate global cerebral blood flow. Count rates detected over the chest were corrected for chest wall contribution and used as arterial input function. A neonatal blood-brain partition coefficient of Xenon was used for the calculation of a mean flow estimator (CBF-infinity). The technique was internally validated by use of differently obtained arterial input functions. In 11 infants without respiratory distress, CBF-infinity was 19.8 ml/100 g/min +/- 5.3 SD. In 24 infants treated with mechanical ventilation CBF-infinity was 11.8 ml/100 g/min +/- 3.2 SD. In 7 infants treated with continuous positive airway pressure CBF-infinity was 21.3 ml/100 g/min +/- 12.0 SD. When the reduction of CBF-infinity associated with mechanical ventilation was taken into account, the 9 infants with subependymal/intraventricular haemorrhage had increased CBF-infinity. The effects of gestational age, birthweight, mode of delivery, postnatal age, mean arterial blood pressure, PaCO2, blood haemoglobin and phenobarbitone medication were also analysed and found inconsistent. In conclusion, CBF was lower than expected and in infants requiring mechanical ventilation the values were lower still.

Cerebrovascular Circulation↗

Comparison of different indices of dietary control in phenylketonuria.

Ten different indices of dietary control (IDCs) applied frequently to investigate compliance of phenylketonuric patients were calculated for a set of blood phenylalanine levels for 98 patients in the German Collaborative Study of Children Treated for Phenylketonuria during their first 9 years of life. The results were compared for similarities and differences. Cluster analysis of longitudinal phenylalanine data was introduced to analyse phenylalanine blood levels independent of a priori defined criteria of classification. Three groups of good, intermediate and poor long-term dietary control were identified. Internal validation of the IDCs was corroborated by the high inter-correlations of the indices. External validity was determined by the inter-relations of the WISC-R IQ and the IDCs. The different algorithms of IDCs suggest different clinical conclusions. To facilitate comparisons of results of future research, IDCs should be standardized.

Child↗

Achieving linguistic clarity: a model to aid translations.

An international validation study of selected NANDA nursing diagnoses prompted the development of a linguistic model for standardizing and operationalizing the defining characteristics. The translation of NANDA-approved defining characteristics into Portuguese illuminated problems related to the way that sentences, phrases, and words are used. Defining characteristics were reduced into the simplest linguistic components--words. In Portuguese translation, all of the major NANDA-defining characteristics were classified into two alphabetized lists as single-word phenomena/states or qualifiers. Linguistic standardization permitted similar expressions of the defining characteristics in Portuguese and English.

Linguistics↗

Studying the retention of rural physicians.

Rural communities and policy-makers struggle with efforts to enhance the retention of rural physicians. Research available to guide these efforts is often weak methodologically and thus may be pointing retention efforts in nonproductive directions. This article discusses a range of methodologic issues encountered in rural physician retention studies for the purpose of strengthening future studies. Ideal study approaches to answer causal questions, including questions about the "causes" of rural physician retention, must demonstrate good internal validity, for which chance, bias, and confounding are accounted. Retention studies that rely simply on asking physicians why they stay or leave rural areas can be useful at times, but are too prone to bias and their findings difficult to verify. Simply identifying what physicians find satisfying or dissatisfying about rural work also will not reliably reveal why they stay or leave, a related but still distinct question. Stronger approaches to studying retention include the traditional quantitative study--in which retention factors are identified when they are statistically related to physicians' retention, and the increasingly popular qualitative study--in which retention issues are revealed through prolonged, in-depth interactions with physicians. This article also discusses various definitions of retention, the use of survival curves to present retention findings, and the importance of studying retention in inception cohorts. The benefits and downside of studying retention with prospective and retrospective study designs are described.

Career Mobility↗

In vitro and human testing strategies for skin irritation.

Prior to the manufacture, transport, and marketing of chemicals or products, it is critical to assess their potential for skin toxicity (corrosion or irritation), thereby protecting the worker and consumer from adverse skin effects due to intended or accidental skin exposure. Traditionally, animal testing procedures have provided the data needed to assess the more severe forms of skin toxicity, and current regulations may require animal test data before permission can be obtained to manufacture, transport, or market chemicals or the products that contain them. In recent years, the use of animals to assess skin safety has been opposed by some as inhumane and unnecessary. The conflicting needs of the industrial toxicologist to (1) protect human safety, (2) comply with regulations, and (3) reduce animal testing have led to major efforts to develop alternative, yet predictive, test methods. A variety of in vitro skin corrosion test methods have been developed and several have successfully passed initial international validation. These have included skin or epidermal equivalent assays that have been shown to distinguish corrosive from noncorrosive chemicals. These skin/epidermal equivalent assays have also been modified and used to assess skin irritation potential relative to existing human exposure test data. The data show a good correlation between in vitro assay data and different types of human skin irritation data for both chemicals and consumer products. The effort to eliminate animal tests has also led to the development of a novel human patch test for assessment of acute skin irritation potential. A case study shows the benefits of in vitro and human skin irritation tests compared to the animal tests they seek to replace, and strategies now exist to adequately assess human skin irritation potential without the need to rely on animal test methods.

Animals↗

The development of a comprehensive headache diary--verbal descriptor scales.

A headache diary was developed to allow the ongoing assessment of subjective and behavioural components of headache pain. A modified version of Philips & Hunter's (1981) pain behaviour checklist which assesses three types of pain behaviour was incorporated for the latter. A scale based on pain descriptors was developed for the subjective component. This scale was factor analysed to reveal five aspects of headache pain, two reactive and three sensory. When the descriptors were scaled it was found that the amount of pain represented by some words was significantly greater in headache than non-headache subjects. Within each descriptor factor, the words do not appear to vary in intensity, with the exception of one reactive factor which appears to reflect overall evaluation of pain. Internal validity of the diary was investigated showing distinctive patterns of association between the subjective factors, pain behaviour, and pain intensity. External validity was assessed by the use of the diary in an intervention study and in delineating differences between migraine and tension headache groups.

Adolescent↗

Predictive Models for Hypoglycemia Risk in Haemodialysis Patients With Diabetic Kidney Disease: Systematic Review and Meta-Analysis.

AIM: To provide evidence for selecting and developing reliable clinical assessment tools for hypoglycemia in diabetic kidney disease patients during haemodialysis. DESIGN: Review. METHODS: Systematic searches were performed in 9 Chinese and English databases to collect literature regarding the development of hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease. Two reviewers independently performed literature screening, data extraction, risk-of-bias assessment, and applicability evaluation. The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias and applicability of the included studies. Meta-analysis was conducted using R software. DATA SOURCES: CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase, Web of Science, and CINAHL. The search period covered from the establishment date of each database to December 2025. RESULTS: Six studies, comprising six prediction models, were included. Two studies performed internal validation, and three conducted external validation. All models reported the area under the curve, ranging from 0.813 to 0.866, and calibration measures. Four studies were rated as having a high risk of bias, while all six demonstrated good overall applicability. The meta-analysis showed that the pooled AUC value of the six studies was 0.846 (95% CI: 0.823-0.867). CONCLUSION: Research on hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease remains in the developmental stage. Although the included prediction models exhibited satisfactory apparent discriminatory ability and clinical applicability, most of the original studies suffered from a high risk of bias and lacked adequate validation. The true predictive performance and clinical application value of these models remain to be further verified. Accordingly, routine and unconditional clinical application is not recommended at this stage. Future studies should include more high-quality, multicenter external validation and develop models with high generalizability, favourable clinical applicability, and robust predictive performance to facilitate early identification of hypoglycemia risk in this population. IMPACT: This study systematically evaluated the hypoglycemia risk prediction models for diabetic kidney disease patients during haemodialysis, and the research on hypoglycemia risk prediction models for maintenance haemodialysis patients during dialysis is still in the development stage. This study provides a reference for clinical medical staff to select or develop hypoglycemia risk prediction and assessment tools for diabetic kidney disease patients during haemodialysis. REPORTING METHOD: This study was conducted in accordance with the relevant guidelines of the EQUATOR Network and followed the TRIPOD-SRMA Checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. TRIAL REGISTRATION: PROSPERO: CRD420251243352.

Humans↗

Assessment of the effects of eleutherococcus senticosus on endurance performance.

The use of nutritional ergogenic aids containing Eleutherococcus senticosus (ES), a plant which is also known as ciwujia or Siberian ginseng, is relatively common among endurance athletes. Eleutherococcus senticosus has been suggested to improve cardiorespiratory fitness (CF) and fat metabolism (FAM) and, therefore, endurance performance (EP). This article reviews the studies that evaluated the effects of ES during endurance exercise, three of which suggest that ES substantially improves CF, FAM, and EP. However, each of these reports contains severe methodological flaws, which seriously threaten their internal validity, thereby rendering hazardous the generalization of the results. On the other hand, 5 studies that used rigorous research protocols show no benefit of ES on CF, FAM, and EP. It is therefore concluded that ES supplementation (up to 1000 to 1200 mg/d for 1 to 6 wk) offers no advantage during exercise ranging in duration from 6 to 120 min.

Adult↗

Classification of metabolites with kernel-partial least squares (K-PLS).

Numerous experimental and computational approaches have been developed to predict human drug metabolism. Since databases of human drug metabolism information are widely available, these can be used to train computational algorithms and generate predictive approaches. In turn, they may be used to assist in the identification of possible metabolites from a large number of molecules in drug discovery based on molecular structure alone. In the current study we have used a commercially available database (MetaDrug) and extracted a fraction of the human drug metabolism data. These data were used along with augmented atom descriptors in a predictive machine learning model, kernel-partial least squares (K-PLS). A total of 317 molecules, including parent drugs and their primary and secondary (sequential) metabolites, were used to build these models corresponding to individual metabolism rules, representing the formation of discrete metabolites, e.g., N-dealkylation. Each model was internally validated to assess the capability to classify other molecules that were left out. Using receiver operator curve statistics models for N-dealkylation, O-dealkylation, aromatic hydroxylation, aliphatic hydroxylation, O-glucuronidation, and O-sulfation gave area under the curve values from 0.75 to 0.84 and were able to predict between 61 and 79% active molecules upon leave-one-out testing. This preliminary study indicates that K-PLS and possibly other similar machine learning methods (such as support vector machines) can be applied to predicting human drug metabolite formation in a classification manner. Improvements can be achieved using considerably larger datasets that contain more positive examples for the less frequently occurring metabolite rules, as well as the external evaluation of novel molecules.

Biotransformation↗

Real-time reverse transcription-PCR for detection of rotavirus and adenovirus as causative agents of acute viral gastroenteritis in children.

Viral pathogens are the most common cause of gastroenteritis in developed countries. Human rotavirus and adenovirus infections are major causes of acute outbreaks and sporadic cases of gastroenteritis, occurring primarily among children less than 2 years of age. Patient hospitalization is often required, with enormous infection control implications. This work describes the development of real-time PCR assays for the detection of group F adenovirus, rotavirus A, and rotavirus C from stool specimens. Two hundred twenty stool samples from pediatric patients exhibiting symptoms of diarrhea and/or vomiting were examined. PCR results were compared with those of virus detection by electron microscopy and latex agglutination antigen detection. The incorporation of an internal-control RNA that was spiked into individual stool extracts functioned as an internal validation for the reporting of PCR-negative results. Rotavirus C was not detected by real-time PCR in the patient stool samples examined. Real-time reverse transcription-PCR resulted in 175% and 111% increases in the rates of detection of adenovirus F and rotavirus A, respectively, compared with latex agglutination testing. Molecular detection increased the number of stool specimens in which causative agents of gastroenteritis were identified by 155% compared to electron microscopy. Genotyping of a proportion of the rotavirus and adenovirus strains identified only genotype G1 rotavirus and both adenovirus genotypes 40 and 41 in circulation within the patient cohort examined. The results highlight the significance of rapid molecular methods for the routine screening of stool samples in hospital laboratories to provide rapid definitive diagnoses.

Acute Disease↗

Assessment of MagNA pure LC extraction system for detection of human papillomavirus (HPV) DNA in PreservCyt samples by the Roche AMPLICOR and LINEAR ARRAY HPV tests.

Roche Molecular Systems recently released two PCR-based assays, AMPLICOR and LINEAR ARRAY (LA), for the detection and genotyping, respectively, of human papillomaviruses (HPVs). The manual specimen processing method recommended for use with both assays, AmpliLute, can be time-consuming and labor-intensive and is open to potential specimen cross-contamination. We evaluated the Roche MagNA Pure LC (MP) as an alternative for specimen processing prior to use with either assay. DNA was extracted from cervical brushings, collected in PreservCyt media, by AmpliLute and MP using DNA-I and Total Nucleic Acid (TNA) kits, from 150 patients with histologically confirmed cervical abnormalities. DNA was amplified and detected by AMPLICOR and the LA HPV test. Concordances of 96.5% (139 of 144) (kappa=0.93) and 95.1% (135 of 142) (kappa=0.90) were generated by AMPLICOR when we compared DNA extracts from AmpliLute to MP DNA-I and TNA, respectively. The HPV genotype profiles were identical in 78.7 and 74.7% of samples between AmpliLute and DNA-I or TNA, respectively. To improve LA concordance, all 150 specimens were extracted by MP DNA-I protocol after the centrifugation of 1-ml PreservCyt samples. This modified approach improved HPV genotype concordance levels between AmpliLute and MP DNA-I to 88.0% (P=0.043) without affecting AMPLICOR sensitivity. Laboratories that have an automated MP extraction system would find this procedure more feasible and easier to handle than the recommended manual extraction method and could substitute such extractions for AMPLICOR and LA HPV tests once internally validated.

Cervix Uteri↗

Comparison of three different sensitive assays for hepatitis B virus DNA in monitoring of responses to antiviral therapy.

The aim of our study was to compare the performances of two new hepatitis B virus (HBV) DNA assays, a cross-linking assay (NAXCOR) and a hybrid-capture amplification assay (Digene), versus the widely used branched-DNA (bDNA) assay (Chiron) in the monitoring of HBV DNA levels during antiviral treatment. Serial serum samples from 12 chronically HBV infected patients undergoing a phase II trial of an antiviral drug, 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), were studied. A total of 96 serum samples were tested for HBV DNA using the cross-linking, hybrid-capture amplification, and bDNA assays. In the comparison of the cross-linking and bDNA assays, concordant results were found in 77 (80.3%) samples, no significant difference was found between the median log(10) HBV DNA levels (6.66 versus 7. 17 meq/ml), and the results of the two assays were closely correlated (r = 0.95). In the comparison of the hybrid-capture amplification and bDNA assays, concordant results were found in 79 (82.3%) samples, no significant difference was found between the median log(10) HBV DNA levels (6.98 versus 6.99 meq/ml), and the results of the two assays were closely correlated (r = 0.99). Six (6. 3%) samples by the cross-linking assay and 10 (10.4%) samples by the bDNA assay required retesting because of unacceptably high within-run coefficients of variance. No sample required retesting in the hybrid-capture amplification assay according to the internal validation. In conclusion, the cross-linking and hybrid-capture amplification assays were as sensitive as the bDNA assay for HBV DNA detection and can be recommended for monitoring of HBV DNA levels during antiviral treatment.

Antiviral Agents↗

"UnPAKing" human immunodeficiency virus (HIV) replication: using small interfering RNA screening to identify novel cofactors and elucidate the role of group I PAKs in HIV infection.

In order to identify novel proviral host factors involved in human immunodeficiency virus (HIV) infection, we performed a screen of a small interfering RNA (siRNA) library targeting 5,000 genes with the highest potential for being targets for therapeutics. Many siRNAs in the library against known host factors, such as TSG101, furin, and CXCR4, were identified as inhibitors by the screen and thus served as internal validation. In addition, many novel factors whose knockdown inhibited infection were identified, including Pak3, a member of the serine/threonine group I PAK kinases. The HIV accessory factor Nef has been shown to associate with a PAK kinase, leading to enhanced viral production; however, the exact identity of the kinase has remained controversial. Prompted by the Pak3 screen hit, we further investigated the involvement of group I PAK kinases in HIV using siRNA. Contrary to the current literature, Pak1 depletion strongly inhibited HIV infection in multiple cell systems and decreased levels of integrated provirus, while Pak2 depletion showed no effect. Overexpression of a constitutively active Pak1 mutant also enhanced HIV infection, further supporting its role as the dominant PAK involved.

Gene Expression Regulation, Viral↗

Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs.

A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.

Anti-Inflammatory Agents, Non-Steroidal↗