Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk

BackgroundUsing novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis. MethodThe study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell’s C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia. ResultsA total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3–3.6). External validation indicated strong performance on unseen data (Harrell’s C 0.85, 95% CI 0.84–0.86), an increase of 0.06 from the original model. ConclusionsUsing NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.     

A prospective investigation of depression and adverse outcomes in patients undergoing vascular surgical interventions: A retrospective cohort study using a large mental health database in South London

BackgroundPatients with depression are more susceptible to cardiovascular illness including vascular surgeries. However, health outcomes after vascular surgery among patients with depression is unknown. This study aimed to investigate associations of depression with post-operative health outcomes for vascular surgical patients.MethodsA retrospective observational study was conducted using data from a large mental healthcare provider and linked national hospitalization data for the same south London geographic catchment. OPCS-4 codes were used to identify vascular procedures. Health outcomes were compared between those with/without depression including length of hospital stay (LOS), inpatient mortality, and 30 day emergency hospital readmissions. Predictors of these health outcomes were also assessed.ResultsVascular surgery was received by 9,267 patients, including 446 diagnosed with depression. Patients with depression had a higher risk of emergency admission for vascular surgery (odds ratio [OR] 1.28; 1.03, 1.59), longer index LOS (IRR 1.38; 1.33–1.42), and a higher risk of 30-day emergency readmission (OR 1.82; 1.35–2.47). Patients with depression had higher inpatient mortality after adjustment for sociodemographic status (1.51; 1.03, 2.23) but not on full adjustment, and had longer emergency readmission LOS (1.13; 1.04, 1.22) after adjustment for sociodemographic factors and cardiovascular disease. Correlates of vascular surgery hospitalization among patients with depression included admission through emergency route for longer LOS, inpatient mortality, and 30-day hospital readmission.ConclusionPatients with depression undergoing vascular surgery have substantially poorer health outcomes. Screening for depression prior to surgery might be indicated to target preventative measures.     

Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer

Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA.     

Establishing and managing a periodontal biobank for research: the sharing of experience

Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.     

The immune response in two populations of wild badgers naturally infected with bovine tubercle bacilli

This study describes the immune responses of two defined badger populations; one from East Sussex and another from Staffordshire. The mean in vitro lymphoproliferative response, of all infected badgers from both areas, to Glaxo BCG, was significantly greater than that of healthy animals. The infected badgers had significantly higher antibody levels against mycobacterial antigens, especially New Tuberculin, than did the healthy animals. All the healthy and tuberculous badgers from the Staffordshire area were invariably unreactive to the various preparations used for skin-testing. However, in the East Sussex area, positive reactions were obtained in 10 out of 37 healthy and 7 out of 10 infected animals. This is the first account of positive skin tests in free living badgers. These results support the concept that badgers infected with bovine tubercle bacilli pass through an immunological spectrum throughout much of which they are unlikely to be important sources of infection. In the early stages, tubercle bacilli are excreted from infected wounds, whereas in the later stages, failure of cell-mediated immunity results in excretion of tubercle bacilli from other sites and the badger becomes a potent source of infection.     

FGFR2, HER2 and cMet in gastric adenocarcinoma: detection,prognostic significance and assessment of downstream pathway activation

Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 % of cases and associated with worse survival (P?=?0.005). HER2 overexpression was observed in 10 % of cases and associated with increased survival (P?=?0.041). cMet overexpression was observed in 4 % of cases and associated with worse survival (P?<?0.001). On multivariate analysis, only cMet retained significance (P?=?0.006). pS6 and pERK expression were observed in 73 % and 30 % of tumours, respectively, with no association with survival. HER2 (P?=?0.004) and pERK (P?=?0.001) expression differed between tumour regions with HER2 expression increased in the LS compared with the TB and IE. These findings confirm subpopulations in gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials.     

Should Athletes Return to Activity After Cryotherapy?

Reference/Citation

Bleakley CM, Costello JT, Glasgow PD. Should athletes return to sport after applying ice? A systematic review of the effect of local cooling on functional performance. Sports Med. 2012; 42(1):69–87.

Clinical Question

Does local tissue cooling affect immediate functional performance outcomes in a sport situation?

Data Sources

Studies were identified by searching MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE, each from the earliest available record through April 2011. Combinations of 18 medical subheadings or key words were used to complete the search.

Study Selection

This systematic review included only randomized controlled trials and crossover studies published in English that examined human participants who were treated with a local cooling intervention. At least 1 functional performance outcome that was measured before and after a cooling intervention had to be reported. Excluded were studies using whole-body cryotherapy or cold-water immersion above the waist and studies that measured strength or force production during evoked muscle contraction.

Data Extraction

Data were extracted by 2 authors using a customized form to evaluate relevant data on study design, eligibility criteria, detailed characteristics of cooling protocols, comparisons, and outcome measures. Disagreement was resolved by consensus or third-party adjudication. To perform an intent-to-treat analysis when possible, data were extracted according to the original allocation groups, and losses to follow-up were noted. The review authors were not blinded to the study author, institution, or journal. For each study, mean differences or standardized mean differences and 95% confidence intervals were calculated for continuous outcomes using RevMan (version 5.1; The Nordic Cochrane Centre, Copenhagen, Denmark). Treatment effects were based on between-groups comparisons (cryotherapy versus control) using postintervention outcomes or within-group comparisons (precryotherapy versus postcryotherapy). If continuous data were missing standard deviations, other statistics including confidence intervals, standard error, t values, P values, or F values were used to calculate the standard deviation. The Cochrane risk-of-bias tool was used to assess the methodologic quality of included studies. Each study was evaluated for sequence generation, allocation concealment, assessor blinding, and incomplete outcome data. Studies were graded as low or high based on the criteria met, but the risk of bias across the studies was consistently high, so meaningful subgroup classifications were not possible. Differences in study quality and intervention details, including duration of cryotherapy interventions and time periods after intervention before follow-up, were potential sources of bias and considered for a subgroup analysis.

Main Results

Using the search criteria, the authors originally identified 1449 studies. Of these, after title and abstract review, 99 studies were deemed potentially relevant and kept for further analysis (1350 studies were excluded). Of the 99 potentially relevant studies, 35 were included in the final review (64 studies were excluded), with relevant outcomes of strength, power, vertical jump, endurance, agility, speed, performance accuracy, and dexterity reported. The 64 excluded studies were rejected due to intervention relevancy, outcome relevancy, and non-English language. In the 35 studies meeting the inclusion criteria, 665 healthy participants were assessed. Muscle strength (using an isokinetic dynamometer, cable tensiometer, strain-gauge device, or load cell) was assessed in 25 studies, whole-body exercise (vertical jump height, power, timed hop test, sprint time, and time taken to complete running-based agility tests, including carioca runs, shuttle sprints, T-shuttle, and cocontraction tests) was assessed in 6, performance accuracy (throwing or shooting) was assessed in 2, and hand dexterity was assessed in 2. Outcomes before and immediately after cryotherapy intervention were reported in all studies; additional outcome assessments at times ranging from 5 to 180 minutes postintervention were recorded in 11 studies. The review authors reported a high risk of bias: selection bias (poor randomization and concealment of group allocation), performance and detection bias (poor blinding of assessors), and attrition bias (incomplete data). Because of the diversity of studies, particularly with respect to cryotherapy protocols and the potential for rewarming before the posttest, the effects of cryotherapy on functional performance were mixed. From the included studies, the authors concluded that cryotherapy treatment reduced upper and lower extremity muscle strength immediately after cryotherapy. However, increases in force output after cryotherapy were reported in 5 studies. Regardless of the effect of cryotherapy on strength, the clinical meaningfulness of most of the data may not be important due to variability and small effects. Studies reporting outcomes of muscle endurance resulted in conflicting evidence: endurance increased immediately after cryotherapy in 6, whereas muscle endurance decreased in 3 . These conflicting results limit the ability to draw clinically relevant conclusions about the effect of cryotherapy on muscle endurance. The majority of studies evaluating whole-body exercise demonstrated decreases in performance after cryotherapy; these outcomes included vertical jump, sprint, and agility, even when cryotherapy was applied only to a body part. Additionally, cryotherapy appeared to decrease hand dexterity and throwing accuracy immediately after intervention, although an increase in shooting performance postintervention was reported in 1 study .

Conclusions

The authors suggested that the available evidence indicates that athletic performance may be adversely affected when athletes return to play immediately after cryotherapy treatments. Many of the included studies used variable cooling protocols, reflecting differences in time, temperature, and mode of cryotherapy. The majority of the included studies used cryotherapy for at least 20 minutes. However, when considering an immediate return to activity, this cooling duration may not be clinically relevant because cryotherapy applications during practice and competitions usually last less than 20 minutes. When immediate return to activity occurs after cryotherapy, short-duration cold applications or progressive warm-ups should be implemented to prevent a deleterious effect on functional performance.Key Words: cold modalities, functional performance, strength, endurance