Revealing patient-reported experiences in healthcare from social media using thedesign-acquire-process-model-analyse-visualise framework.

Understanding patient experience in healthcare is increasingly important and desired by medical professionals in a patient-centred care approach. Healthcare discourse on social media presents an opportunity to gain a unique perspective on patient-reported experiences, complementing traditional survey data. These social media reports often appear as first-hand accounts of patients' journeys through the healthcare system, whose details extend beyond the confines of structured surveys and at a far larger scale than focus groups. However, in contrast with the vast presence of patient-experience data on social media and the potential benefits the data offers, it attracts comparatively little research attention due to the technical proficiency required for text analysis. In this article, we introduce the design-acquire-process-model-analyse-visualise framework to provide an overview of techniques and an approach to capture patient-reported experiences from social media data. We apply this framework in a case study on prostate cancer data from /r/ProstateCancer, demonstrate the framework's value in capturing specific aspects of patient concern (such as sexual dysfunction), provide an overview of the discourse, and show narrative and emotional progression through these stories. We anticipate this framework to apply to a wide variety of areas in healthcare, including capturing and differentiating experiences across minority groups, geographic boundaries, and types of illnesses.

Advanced statistics identification of participant and treatment predictors associated with severe adverse effects induced by fluoropyrimidine-based chemotherapy.

PURPOSE: Adverse effects following fluoropyrimidine-based chemotherapy regimens are common. However, there are no current accepted diagnostic markers for prediction prior to treatment, and the underlying mechanisms remain unclear. This study aimed to determine genetic and non-genetic predictors of adverse effects. METHODS: Genomic DNA was analyzed for 25 single nucleotide polymorphisms (SNPs). Demographics, comorbidities, cancer and fluoropyrimidine-based chemotherapy regimen types, and adverse effect data were obtained from clinical records for 155 Australian White participants. Associations were determined by bivariate analysis, logistic regression modeling and Bayesian network analysis. RESULTS: Twelve different adverse effects were observed in the participants, the most common severe adverse effect was diarrhea (12.9%). Bivariate analysis revealed associations between all adverse effects except neutropenia, between genetic and non-genetic predictors, and between 8 genetic and 12 non-genetic predictors with more than 1 adverse effect. Logistic regression modeling of adverse effects revealed a greater/sole role for six genetic predictors in overall gastrointestinal toxicity, nausea and/or vomiting, constipation, and neutropenia, and for nine non-genetic predictors in diarrhea, mucositis, neuropathy, generalized pain, hand-foot syndrome, skin toxicity, cardiotoxicity and fatigue. The Bayesian network analysis revealed less directly associated predictors (one genetic and six non-genetic) with adverse effects and confirmed associations between six adverse effects, eight genetic predictors and nine non-genetic predictors. CONCLUSION: This study is the first to link both genetic and non-genetic predictors with adverse effects following fluoropyrimidine-based chemotherapy. Collectively, we report a wealth of information that warrants further investigation to elucidate the clinical significance, especially associations with genetic predictors and adverse effects.

A multivariate extension to the standard 4σ criterion for comparison of forensic glass evidence.

This manuscript presents a more accurate and easy to implement multivariate generalisation of the international standard 4σ forensic glass comparison technique. Many crimes result in glass breaking, and the broken glass found at a crime scene can be important forensic evidence. The chemical composition of this glass can be measured to establish whether it can be distinguished from glass fragments found on a suspect's clothing. The chemical composition can be measured using laser ablation-inductively coupled plasma mass spectrometry. A commonly used method to compare fragments of glass is the 4σ interval criterion. This method, however, compares each element individually and does not take advantage of the multivariate nature of this data. We introduce a multivariate extension to this method, which makes use of the correlation structure between the elements. We demonstrate that this method results in an improvement in the false positive rate, with only a small compromise in the false negative rate. The improvement in false positive rate is desirable as false positives translate to misleading evidence against a potentially innocent defendant. The multivariate generalisation improves accuracy while retaining a similar interpretation, and so is suitable to present in court.

Long-term outcome of kidney transplant by using restored kidney grafts after tumour ex vivo excision - a prospective study.

The aim of this study is to report long-term outcomes of kidney transplantation by using the kidney graft after a small tumour ex vivo excision. A structured programme was established to use the restored kidney graft from urological referral after radical nephrectomy. The criteria were defined as tumour size ≤3 cm, margin clear on frozen section and recipients aged ≥60 years or those on the urgent list for transplantation as a result of imminent lack of dialysis access. The recipients were followed up regularly for surveillance of tumour recurrence. Between February 2007 and February 2018, 28 recipients had kidney transplantation by using the restored kidney grafts. The tumour size was 2.6 ± 0.7 cm. The follow-up was median 7 years without evidence of tumour recurrence. The patient and graft survival was satisfactory. Kidney transplantation by using restored kidneys after a small tumour excision is a novel source for selected recipients. The long-term patient and graft survival is satisfactory. Although there is a risk of tumour recurrence, it is rare event. Together with literature review, we would support use of kidney graft after a small tumour excision for selected recipients.

Relationship between allograft cyclosporin concentrations and P-glycoprotein expression in the 1st month following renal transplantation.

The immunosuppressant cyclosporin is a P-glycoprotein (P-gp) substrate whose impaired function has been associated with an increased risk of cyclosporin-induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P-gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression. Blood cyclosporin concentrations (2 hours postdose) were obtained from clinical records, matching allograft cyclosporin concentrations were measured in frozen biopsy tissue by liquid chromatography-tandem mass spectrometry, and allograft P-gp expression was assessed by immunohistochemistry. Blood and allograft cyclosporin concentrations in the 1st month post-transplantation ranged from 505-2005 µg/L and 0.01-16.7 ng/mg tissue, respectively. Dose was the only significant predictor of allograft cyclosporin concentrations (adjusted R2  = .24, F-statistic = 11.52, P = .0019), with no effect of P-gp expression or blood cyclosporin concentrations. P-gp expression is not the major determinant of allograft cyclosporin concentrations.

Mitigation of electroencephalographic and cardiovascular responses to castration in Bos indicus bulls following the administration of either lidocaine or meloxicam.

OBJECTIVE: To investigate the mitigating effects of administration of local anaesthetic or systemic meloxicam on the electroencephalographic (EEG) and cardiovascular responses during surgical castration of Bos indicus bull calves. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: Thirty-six 6-8 month-old Bos indicus bull calves, with a mean ± standard deviation weight of 237 ± 19 kg. METHODS: Animals were allocated randomly to three groups of 12 (group L, 260 mg of 2% lidocaine subcutaneously and intratesticularly 5 minutes prior to castration; group M, 0.5 mg kg-1 of meloxicam subcutaneously 30 minutes prior to castration; group C, no preoperative analgesia administered). Anaesthesia was induced and maintained with halothane (0.9-1.1%) in oxygen. Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded for 300 seconds prior to (baseline, B) and from the start of surgery (first testicle removal, T1). HR and MAP were compared at 10 second intervals for 90 seconds from the start of T1. Median frequency (F50), spectral edge frequency (F95) and total power of the EEG (Ptot) were analysed using area under the curve comparing T1 to B. RESULTS: All EEG variables were significantly different between B and T1 (p ≤ 0.0001). No differences in F50 were found between groups during T1 (p = 0.6491). F95 and Ptot were significantly different between group L and groups C and M during T1 (p = 0.0005 and 0.0163, respectively). There were transient significant changes in HR and MAP in groups L and M compared to group C during the 20-50 second periods. CONCLUSIONS: The EEG changes indicate nociceptive responses in all three groups during surgical castration, greater in group L compared to groups C and M. Both analgesics attenuated the peracute cardiovascular response. Lidocaine and meloxicam administered prior to castration attenuated these responses in Bos indicus bull calves. CLINICAL RELEVANCE: These findings provide support for the preoperative administration of lidocaine and potentially meloxicam for castration in Bos indicus bull calves.

ASXL1 and BIM germ line variants predict response and identify CML patients with the greatest risk of imatinib failure.

Scoring systems used at diagnosis of chronic myeloid leukemia (CML), such as Sokal risk, provide important response prediction for patients treated with imatinib. However, the sensitivity and specificity of scoring systems could be enhanced for improved identification of patients with the highest risk. We aimed to identify genomic predictive biomarkers of imatinib response at diagnosis to aid selection of first-line therapy. Targeted amplicon sequencing was performed to determine the germ line variant profile in 517 and 79 patients treated with first-line imatinib and nilotinib, respectively. The Sokal score and ASXL1 rs4911231 and BIM rs686952 variants were independent predictors of early molecular response (MR), major MR, deep MRs (MR4 and MR4.5), and failure-free survival (FFS) with imatinib treatment. In contrast, the ASXL1 and BIM variants did not consistently predict MR or FFS with nilotinib treatment. In the imatinib-treated cohort, neither Sokal or the ASXL1 and BIM variants predicted overall survival (OS) or progression to accelerated phase or blast crisis (AP/BC). The Sokal risk score was combined with the ASXL1 and BIM variants in a classification tree model to predict imatinib response. The model distinguished an ultra-high-risk group, representing 10% of patients, that predicted inferior OS (88% vs 97%; P = .041), progression to AP/BC (12% vs 1%; P = .034), FFS (P < .001), and MRs (P < .001). The ultra-high-risk patients may be candidates for more potent or combination first-line therapy. These data suggest that germ line genetic variation contributes to the heterogeneity of response to imatinib and may contribute to a prognostic risk score that allows early optimization of therapy.

Synergistic influence of collagen I and BMP 2 drives osteogenic differentiation of mesenchymal stem cells: A cell microarray analysis.

Cell microarrays are a novel platform for the high throughput discovery of new biomaterials. By re-creating a multitude of cell microenvironments on a single slide, this approach can identify the optimal surface composition to drive a desired cell response. To systematically study the effects of molecular microenvironments on stem cell fate, we designed a cell microarray based on parallel exposure of mesenchymal stem cells (MSCs) to surface-immobilised collagen I (Coll I) and bone morphogenetic protein 2 (BMP 2). This was achieved by means of a reactive coating on a slide surface, enabling the covalent anchoring of Coll I and BMP 2 as microscale spots printed by a robotic contact printer. The surface between the printed protein spots was passivated using poly (ethylene glycol) bisamine 10,000Da (A-PEG). MSCs were then captured and cultured on array spots composed of binary mixtures of Coll I and BMP 2, followed by automated image acquisition and quantitative, multi-parameter analysis of cellular responses. Surface compositions that gave the highest osteogenic differentiation were determined using Runx2 expression and calcium deposition. Quantitative single cell analysis revealed subtle concentration-dependent effects of surface-immobilised proteins on the extent of osteogenic differentiation obscured using conventional analysis. In particular, the synergistic interaction of Coll I and BMP 2 in supporting osteogenic differentiation was confirmed. Our studies demonstrate the value of cell microarray platforms to decipher the combinatorial interactions at play in stem cell niche microenvironments.

Predictive model for risk of severe gastrointestinal toxicity following chemotherapy using patient immune genetics and type of cancer: a pilot study.

PURPOSE: Severe chemotherapy-induced gastrointestinal toxicity (CIGT) is common and results in treatment delays, dose reductions, and potential premature treatment discontinuation. Currently, there is no diagnostic marker to predict CIGT. Proinflammatory cytokines, produced via toll-like receptor signaling, are key mediators of this toxicity. Hence, this pilot study investigated the association between immune genetic variability and severe CIGT risk. METHODS: Genomic DNA from 34 patients (10 with severe CIGT) who had received 5-fluoruracil-based chemotherapy regimens was analyzed for variants of IL-1B, IL-2, IL-6, IL-6R, IL-10, TNF-a, TGF-b, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, and OPRM1. Multivariate logistic regression created a prediction model of severe CIGT risk. RESULTS: There were no significant differences between patients with and without severe CIGT with regards to age, sex, type of cancer, or chemotherapy treatment regimens. The prediction model of severe CIGT risk included TLR2 and TNF-a genetic variability and cancer type (colorectal and gastric). This prediction model was both specific and sensitive, with a receiver operator characteristic area under the curve of 87.3 %. CONCLUSIONS: This is the first report of immune genetic variability, together with cancer type, being predictive of severe CIGT risk. These outcomes are being validated in a larger patient population.

Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study.

OBJECTIVE: This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl. METHODS: CYP3A4*22 and CYP3A5*3 polymorphisms were analysed in 620 cancer pain patients receiving transdermal fentanyl (12.5-700 µg/h) from the European Pharmacogenetic Opioid Study. Using stepwise linear regression, CYP3A4/5 genetic variability was examined in combination with patient factors relating to organ drug elimination function and ABCB1 genetics for their association with serum fentanyl and norfentanyl concentrations and metabolic ratio (MR) (norfentanyl : fentanyl). RESULTS: Delivery rate-adjusted serum fentanyl concentrations (0.0012-1.1 nmol/l/µg.h) and MRs (0.08-499) varied widely. Only 43% of variability in serum fentanyl concentrations was accounted for by delivery rate and less than 50% by CYP3A4/5 genotypes and clinical variables (delivery rate, sex, comedications, kidney disease, BMI, serum albumin). CYP3A4*22 and CYP3A5*3 variants, CYP3A inhibitors and variables relating to liver and kidney function (serum albumin, glomerular filtration rate, kidney disease, BMI) were associated with MR, but accounted for only 14% of variability. CONCLUSION: Serum fentanyl concentrations and MR vary considerably between cancer pain patients on transdermal fentanyl patches. CYP3A4*22 and CYP3A5*3 genotypes, and multiple clinical factors, combine to influence transdermal fentanyl pharmacokinetics, but accounted for only a small proportion of variability in this study. Identification of the remaining factors determining serum fentanyl concentrations, and their relationship to efficacy and adverse effects may aid in improving the safety and effectiveness of transdermal fentanyl.

Thermal and mechanical nociceptive threshold testing in pregnant sheep.

OBJECTIVE: Analgesic regimes were compared in pregnant ewes after laparotomy by measuring thermal (TT) and mechanical (MT) nociceptive thresholds. STUDY DESIGN: Prospective randomised experimental study. ANIMALS: Pregnant ewes at 121 days gestation underwent laparotomy as part of another research project. METHODS: Thermal and mechanical thresholds were measured before, and 2, 6, 24 and 48 hours after surgery. Thermal stimuli were delivered to the lateral aspect of the metatarsus via a skin-mounted probe, and mechanical stimuli to the contralateral site via a pneumatically driven 1.5 mm diameter pin. Each test was performed five times, alternating thermal and mechanical stimuli, with ten minutes between thermal stimuli. At the end of surgery ewes received either: 75 µg hour(-1) transdermal fentanyl patch (medial thigh) (group FP) (n = 8), or 3 µg kg(-1 ) hour(-1) intra-peritoneal medetomidine via an osmotic pump (group IPM) (n = 8) inserted immediately prior to closure. Data were analysed using the Kruskal-Wallis RS Test (p < 0.05). Once a significant effect was identified, pairwise comparisons were performed using paired Wilcoxon RS tests. To compensate for multiple hypotheses testing, p < 0.005 was considered significant. RESULTS: Prior to surgery mean ± SD TT was 56.1 ± 5.0 °C (FP) and 55.6 ± 5.0 °C (IPM); MT was 5.3 ± 2.6 N (FP) and 8.0 ± 5.0 N (IPM). In FP there was no significant change in either TT or MT over time. In IPM there was no significant change in MT over time but TT increased at two hours to 59.2 ± 3.0 °C (p = 0.003). Skin temperature (ST) ranged from 33.0 to 34.7 °C and did not change over time. There were no significant differences between groups in TT, MT or ST. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of intra-peritoneal medetomidine (3 µg kg(-1 ) hour(-1) ) by an osmotic pump increases the thermal nociceptive threshold in the immediate post operative period in pregnant sheep, suggesting that this agent may have a role in providing post-operative analgesia.