Evaluating Transperineal Prostate Biopsies Performed by a New Operator: A Prospective Clinical Audit at Dorset County Hospital.

Introduction The transperineal (TP) approach for prostate biopsy offers advantages such as a low risk of infection, the ability to target lesions in difficult locations, and a rapid acquisition of proficiency. This prospective clinical audit aims to evaluate the outcomes and patient experiences of TP prostate biopsies performed by a new operator to determine the feasibility of adopting the TP biopsy as the primary method for prostate evaluations. Methods The study included all patients who underwent a TP prostate biopsy from August 1 to September 30, 2022, at Dorset County Hospital National Health Service Foundation Trust. The operator, a member of the urology team, had recently begun performing these biopsies independently after completing a four-month supervised training program and receiving approval from two consulting trainers. The biopsy technique was evaluated based on diagnostic yield and patient experience, comparing pre-procedure imaging results with histology reports and analyzing patient-completed questionnaires. Results Among the 42 patients, the cancer detection rate was 79%. The highest core positivity rate was 100% in two patients (5%), with 90% in 11 patients (26%). Of the patients, 57% showed complete agreement between magnetic resonance imaging findings and histology. A questionnaire assessing patient experience received a 64% response rate. The most common pain score reported was 2 (on a scale of 0-10), noted in 25% of patients. Most reported mild lower urinary tract symptoms (88%) and mild hematuria (85%). Of the patients, 44% rated their overall satisfaction as 10 (on a scale of 0-10), and no urinary tract infections were reported. Conclusion The findings support the adoption of TP biopsy as the primary method for prostate biopsies due to its short learning curve, high diagnostic yield, and favorable patient satisfaction. Training for new operators should be encouraged to achieve this goal.

Use of Prospective Multiplex Immunohistochemistry to Redefine Tissue Pathways of Diagnostic Core Biopsy of Prostate.

The incidence of prostatic cancer in the United Kingdom has increased over 40% in the past 30 years. The majority of these cancers are diagnosed by core biopsy, posing a considerable strain on a service that struggles to recruit sufficient histopathologists. The current methodology for tissue diagnosis has a significant false-negative rate, small false-positive rate, and a proportion of indeterminate diagnoses. Therefore, this area presents an opportunity both to improve diagnostic quality and to reduce the burden on resources. We investigated streamlining tissue pathways by increasing the utilization of readily available resources to reduce the burden on scarce resources and improve the accuracy of diagnosis. This involved applying prospective multiplex immunohistochemistry (IHC) using 4 different markers (CK5, p63, racemase, and Ki-67) and 2 chromogens. We conducted a prospective study using over 8000 cores and 3 consultant histopathologists. The pathologists assessed each core using either conventional stains (hematoxylin and eosin) only or multiplex IHC only. The results of this assessment were later compared with the overall assessment made for the final histologic diagnosis. Results show that IHC alone has a positive predictive value of 98.97% and a negative predictive value of 99.91%, while hematoxylin and eosin alone has a positive predictive value of 94.21% and negative predictive value of 99.07%, demonstrating improved diagnostic accuracy. When assessed against the use of on-demand IHC, prospective IHC improves turn-around-times, reduces indeterminate diagnoses, improves pathologist's accuracy and efficiency and, in overall terms, is cost-effective. In addition, it is possible to structure these tests within the routine of a diagnostic service with little impact on the overall capacity of the laboratory.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience.

BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason

Focal HIFU therapy for anterior compared to posterior prostate cancer lesions.

OBJECTIVE: To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. MATERIALS AND METHODS: In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6-12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. RESULTS: 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). CONCLUSION: Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours.

An Exploratory Study of Dose Escalation vs Standard Focal High-Intensity Focused Ultrasound for Treating Nonmetastatic Prostate Cancer.

Objective: Analysis of treatment success regarding oncological recurrence rate between standard and dose escalation focal high-intensity focused ultrasound (HIFU) of prostate cancer. Materials and Methods: In this analysis of our prospectively maintained HIFU (Sonablate® 500) database, 598 patients were identified who underwent a focal HIFU (Sonablate 500) between March 2007 and November 2016. Follow-up occurred with 3-monthly clinic visits and prostate specific antigen (PSA) testing in the first year. Thereafter, PSA was measured 6-monthly or annually at least. Routine and for-cause multiparametric MRI (mpMRI) was conducted with biopsy for MRI suspicion of recurrence. Treatments were delivered in a quadrant or hemiablation fashion depending on the gland volume as well as tumor volume and location. Before mid-2015, standard focal HIFU was used (two HIFU blocks); after this date, some urologists conducted dose escalation focal HIFU (three overlapping HIFU blocks). Propensity matching was used to ensure two matched groups, leading to 162 cases for this analysis. Treatment failure was defined by any secondary treatment (systemic therapy, cryotherapy, radiotherapy, prostatectomy, or further HIFU), metastasis from prostate cancer without further treatment, tumor recurrence with Gleason score ≥7 (≥3 + 4) on prostate biopsy without further treatment, or prostate cancer-related mortality. Complications and side-effects were also compared. Results: Median age was 64.5 years (interquartile range [IQR] 60-73.5) in the standard focal-HIFU group and 64.5 years (IQR 60-69) in the dose-escalation group. Median prostate volume was 37 mL (IQR 17-103) in the standard group and 47.5 mL (IQR 19-121) in the dose-escalation group. As tumor volume on mpMRI and Gleason score were major matching criteria, these were identical with 0.43 mL (IQR 0.05-2.5) and Gleason 3 + 3 = 6 in 1 out of 32 (3%), 3 + 4 = 7 in 27 out of 32 (84%), and 4 + 3 = 7 in 4 out of 32 (13%). Recurrence in treated areas was found in 10 out of 32 (31%) when standard treatment zones were applied, and in 6 out of 32 (19%) of dose-escalation focal HIFU (p = 0.007). Conclusion: This exploratory study shows that dose escalation focal HIFU may achieve higher rates of disease control compared with standard focal HIFU. Further prospective comparative studies are needed.

Evaluation of functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) procedure in men with primary localized, non-metastatic prostate cancer: results from the HIFU Evaluation and Assessment of Treatment (HEAT) registry.

OBJECTIVES: To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. PATIENTS AND METHODS: In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. RESULTS: Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. CONCLUSION: A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

Prostate Specific Antigen Criteria to Diagnose Failure of Cancer Control following Focal Therapy of Nonmetastatic Prostate Cancer Using High Intensity Focused Ultrasound.

PURPOSE: We determined whether prostate specific antigen criteria after focal high intensity focused ultrasound to treat prostate cancer could diagnose treatment failure. MATERIALS AND METHODS: A total of 598 patients in a prospectively maintained national database underwent focal high intensity focused ultrasound with a Sonablate® 500 device from March 2007 to November 2016. Followup consisted of 3-month clinic visits and prostate specific antigen testing in year 1 with prostate specific antigen measurement every 6 to 12 months and multiparametric magnetic resonance imaging with biopsy for magnetic resonance imaging suspicious for recurrence. Treatment failure was considered any secondary treatment, tumor recurrence with Gleason 3 + 4 or greater disease on prostate biopsy without further treatment or metastasis and/or prostate cancer related mortality. To diagnose failure we evaluated a series of nadir + x thresholds with x values of 0.1 to 2.0 ng/ml. RESULTS: Median patient age was 65 years (IQR 60-71) and the median Gleason score was 7 (range 6-9). Gleason 3 + 4 or greater disease was present in 80% of cases. Tumors were radiologically staged as T1c-T2c in 522 of the 596 patients (88%) and as T3a/b in 74 (12.4%). Baseline median prostate specific antigen was 7.80 ng/ml (IQR 5.96-10.45) in failed cases and 6.77 ng/ml (IQR 2.65-9.71) in cases without failure. Optimal performance according to the Youden index to indicate the most appropriate nadir + x at all analyzed time points at 3-month intervals showed that nadir + 1.0 ng/ml would have 27.3% to 100% sensitivity and 39.4% to 85.6% specificity depending on the time of evaluation in the first 3 years. Nadir + 1.5 ng/ml showed 18.2% to 100% sensitivity and 60.6% to 91.8% specificity with nadir + 2.0 ng/ml leading to similar sensitivity and specificity ranges. Nadir + 1.0 ng/ml at 12 months and nadir + 1.5 ng/ml at 24 and 36 months had 100% sensitivity and 96.1% to 100% negative predictive value. CONCLUSIONS: Following focal high intensity focused ultrasound a prostate specific antigen nadir of 1.0 ng/ml at 12 months and 1.5 ng/ml at 24 to 36 months might be used to triage men requiring magnetic resonance imaging and biopsy. These data need prospective validation.

Effect of Structure Modifying Agents on the Structural, Morphological and Optical Features of Hydrothermally Grown ZnO.

Morphology of Zinc Oxide (ZnO) is an important parameter to enhance the efficiency of optoelectronic devices. Morphology also plays a significant role in gas sensing properties of ZnO. In this research work, different morphologies of Zinc Oxide including nanorods, disks and flakes were obtained using Zinc Acetate, Sodium Dodecyl Sulphate and Trisodium Citrate as additives to a parent solution of Zinc nitrate hexahydrate (Zn(NO3)2·6H2O) and Hexamethylenetetramine (HMTA, (CH2)6N4) for hydrothermal growth. Use of Zinc Acetate as an additive has been rarely reported. This work presents the ability of Zinc Acetate to transform the morphology of ZnO nanorods to nanoneedles. Furthermore, in this study addition of Sodium Dodecyl Sulphate and Trisodium Citrate to the parent solution has shown potential for growing continuous granular films by the low cost and low temperature hydrothermal technique. Variation in crystallite size and band gap values with increasing concentration of Zinc Acetate, Sodium Dodecyl Sulphate and Trisodium Sulphate has been studied. Films with crystallite sizes of 7.48 nm and 6.77 nm were achieved with 5 mM Sodium Dodecyl Sulphate and 5 mM Trisodium Citrate respectively. The band gap of films produced with 5 mM Sodium Dodecyl Sulphate and with 5 mM Trisodium Citrate were 3.43 eV and 3.45 eV respectively. Therefore hydrothermal growth with Sodium Dodecyl Sulphate or Trisodium Citrate is a potential technique for obtaining granular ZnO films.

Leveraging the Electronic Health Record to Create an Automated Real-Time Prognostic Tool for Peripheral Arterial Disease.

Background Automated individualized risk prediction tools linked to electronic health records ( EHR s) are not available for management of patients with peripheral arterial disease. The goal of this study was to create a prognostic tool for patients with peripheral arterial disease using data elements automatically extracted from an EHR to enable real-time and individualized risk prediction at the point of care. Methods and Results A previously validated phenotyping algorithm was deployed to an EHR linked to the Rochester Epidemiology Project to identify peripheral arterial disease cases from Olmsted County, MN, for the years 1998 to 2011. The study cohort was composed of 1676 patients: 593 patients died over 5-year follow-up. The c-statistic for survival in the overall data set was 0.76 (95% confidence interval [CI], 0.74-0.78), and the c-statistic across 10 cross-validation data sets was 0.75 (95% CI, 0.73-0.77). Stratification of cases demonstrated increasing mortality risk by subgroup (low: hazard ratio, 0.35 [95% CI, 0.21-0.58]; intermediate-high: hazard ratio, 2.98 [95% CI, 2.37-3.74]; high: hazard ratio, 8.44 [95% CI, 6.66-10.70], all P<0.0001 versus the reference subgroup). An equation for risk calculation was derived from Cox model parameters and ß estimates. Big data infrastructure enabled deployment of the real-time risk calculator to the point of care via the EHR . Conclusions This study demonstrates that electronic tools can be deployed to EHR s to create automated real-time risk calculators to predict survival of patients with peripheral arterial disease. Moreover, the prognostic model developed may be translated to patient care as an automated and individualized real-time risk calculator deployed at the point of care.

A comparison of word embeddings for the biomedical natural language processing.

BACKGROUND: Word embeddings have been prevalently used in biomedical Natural Language Processing (NLP) applications due to the ability of the vector representations being able to capture useful semantic properties and linguistic relationships between words. Different textual resources (e.g., Wikipedia and biomedical literature corpus) have been utilized in biomedical NLP to train word embeddings and these word embeddings have been commonly leveraged as feature input to downstream machine learning models. However, there has been little work on evaluating the word embeddings trained from different textual resources. METHODS: In this study, we empirically evaluated word embeddings trained from four different corpora, namely clinical notes, biomedical publications, Wikipedia, and news. For the former two resources, we trained word embeddings using unstructured electronic health record (EHR) data available at Mayo Clinic and articles (MedLit) from PubMed Central, respectively. For the latter two resources, we used publicly available pre-trained word embeddings, GloVe and Google News. The evaluation was done qualitatively and quantitatively. For the qualitative evaluation, we randomly selected medical terms from three categories (i.e., disorder, symptom, and drug), and manually inspected the five most similar words computed by embeddings for each term. We also analyzed the word embeddings through a 2-dimensional visualization plot of 377 medical terms. For the quantitative evaluation, we conducted both intrinsic and extrinsic evaluation. For the intrinsic evaluation, we evaluated the word embeddings' ability to capture medical semantics by measruing the semantic similarity between medical terms using four published datasets: Pedersen's dataset, Hliaoutakis's dataset, MayoSRS, and UMNSRS. For the extrinsic evaluation, we applied word embeddings to multiple downstream biomedical NLP applications, including clinical information extraction (IE), biomedical information retrieval (IR), and relation extraction (RE), with data from shared tasks. RESULTS: The qualitative evaluation shows that the word embeddings trained from EHR and MedLit can find more similar medical terms than those trained from GloVe and Google News. The intrinsic quantitative evaluation verifies that the semantic similarity captured by the word embeddings trained from EHR is closer to human experts' judgments on all four tested datasets. The extrinsic quantitative evaluation shows that the word embeddings trained on EHR achieved the best F1 score of 0.900 for the clinical IE task; no word embeddings improved the performance for the biomedical IR task; and the word embeddings trained on Google News had the best overall F1 score of 0.790 for the RE task. CONCLUSION: Based on the evaluation results, we can draw the following conclusions. First, the word embeddings trained from EHR and MedLit can capture the semantics of medical terms better, and find semantically relevant medical terms closer to human experts' judgments than those trained from GloVe and Google News. Second, there does not exist a consistent global ranking of word embeddings for all downstream biomedical NLP applications. However, adding word embeddings as extra features will improve results on most downstream tasks. Finally, the word embeddings trained from the biomedical domain corpora do not necessarily have better performance than those trained from the general domain corpora for any downstream biomedical NLP task.

Innovative Informatics Approaches for Peripheral Artery Disease: Current State and Provider Survey of Strategies for Improving Guideline-Based Care.

OBJECTIVE: To quantify compliance with guideline recommendations for secondary prevention in peripheral artery disease (PAD) using natural language processing (NLP) tools deployed to an electronic health record (EHR) and investigate provider opinions regarding clinical decision support (CDS) to promote improved implementation of these strategies. PATIENTS AND METHODS: Natural language processing was used for automated identification of moderate to severe PAD cases from narrative clinical notes of an EHR of patients seen in consultation from May 13, 2015, to July 27, 2015. Guideline-recommended strategies assessed within 6 months of PAD diagnosis included therapy with statins, antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and smoking abstention. Subsequently, a provider survey was used to assess provider knowledge regarding PAD clinical practice guidelines, comfort in recommending secondary prevention strategies, and potential role for CDS. RESULTS: Among 73 moderate to severe PAD cases identified by NLP, only 12 (16%) were on 4 guideline-recommended strategies. A total of 207 of 760 (27%) providers responded to the survey; of these 141 (68%) were generalists and 66 (32%) were specialists. Although 183 providers (88%) managed patients with PAD, 51 (25%) indicated they were uncomfortable doing so; 138 providers (67%) favored the development of a CDS system tailored for their practice and 146 (71%) agreed that an automated EHR-derived mortality risk score calculator for patients with PAD would be helpful. CONCLUSION: Natural language processing tools can identify cases from EHRs to support quality metric studies. Findings of this pilot study demonstrate gaps in application of guideline-recommended strategies for secondary risk prevention for patients with moderate to severe PAD. Providers strongly support the development of CDS systems tailored to assist them in providing evidence-based care to patients with PAD at the point of care.

Postoperative bleeding risk prediction for patients undergoing colorectal surgery.

BACKGROUND: There is limited consensus regarding risk factors for postoperative bleeding. The objective of this work was to investigate the capability of machine learning techniques in combination with practice-based longitudinal electronic medical record data for identifying potential new risk factors for postoperative bleeding and predicting patients at high risk of postoperative bleeding. METHODS: A retrospective study was conducted for patients who underwent colorectal surgery 1998-2015 at a single tertiary referral center. Various predictors were extracted from electronic medical record. The outcome of interest was the occurrence of postoperative bleeding within 7 days of surgery. Logistic regression and gradient boosting machine models were trained. Area under the receiver operating curve and area under the precision recall curve were used to evaluate the performance to different models. RESULTS: Of 13,399 cases undergoing colorectal resection, 1,680 (12.5%) experienced postoperative bleeding. A total of 299 variables were evaluated. Logistic regression and gradient boosting machine models returned an area under the receiver operating curve of 0.735 and 0.822 and area under the precision recall curve of 0.287 and 0.423, respectively. In addition to well-known risk factors for postoperative bleeding, nutrition (ranked third), weakness (ranked fifth), patient mobility (ranked sixth), and activity level (ranked eighth) were found to be novel predictors in the gradient boosting machine model based on permutation importance. CONCLUSION: The study identified measures of functional capacity of patient as novel predictors of postoperative bleeding. The study found that risk of postoperative bleeding can be assessed, allowing for better use of human resources in addressing this important adverse event after surgery.

A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer.

BACKGROUND: Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects. OBJECTIVE: To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%). INTERVENTION: Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality. RESULTS AND LIMITATIONS: The median follow-up was 56 mo (interquartile range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98-100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up. CONCLUSIONS: Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects. PATIENT SUMMARY: In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.

Natural language processing of clinical notes for identification of critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) is a complication of advanced peripheral artery disease (PAD) with diagnosis based on the presence of clinical signs and symptoms. However, automated identification of cases from electronic health records (EHRs) is challenging due to absence of a single definitive International Classification of Diseases (ICD-9 or ICD-10) code for CLI. METHODS AND RESULTS: In this study, we extend a previously validated natural language processing (NLP) algorithm for PAD identification to develop and validate a subphenotyping NLP algorithm (CLI-NLP) for identification of CLI cases from clinical notes. We compared performance of the CLI-NLP algorithm with CLI-related ICD-9 billing codes. The gold standard for validation was human abstraction of clinical notes from EHRs. Compared to billing codes the CLI-NLP algorithm had higher positive predictive value (PPV) (CLI-NLP 96%, billing codes 67%, p < 0.001), specificity (CLI-NLP 98%, billing codes 74%, p < 0.001) and F1-score (CLI-NLP 90%, billing codes 76%, p < 0.001). The sensitivity of these two methods was similar (CLI-NLP 84%; billing codes 88%; p < 0.12). CONCLUSIONS: The CLI-NLP algorithm for identification of CLI from narrative clinical notes in an EHR had excellent PPV and has potential for translation to patient care as it will enable automated identification of CLI cases for quality projects, clinical decision support tools and support a learning healthcare system.

Association of Ankle-Brachial Indices With Limb Revascularization or Amputation in Patients With Peripheral Artery Disease.

Importance: The prevalence and morbidity of peripheral artery disease (PAD) are high, with limb outcomes including revascularization and amputation. In community-dwelling patients with PAD, the role of noninvasive evaluation for risk assessment and rates of limb outcomes have not been established to date. Objective: To evaluate whether ankle-brachial indices are associated with limb outcomes in community-dwelling patients with PAD. Design, Setting, and Participants: A population-based, observational, test-based cohort study of patients was performed from January 1, 1998, to December 31, 2014. Data analysis was conducted from July 15 to December 15, 2017. Participants included a community-based cohort of 1413 patients with PAD from Olmsted County, Minnesota, identified by validated algorithms deployed to electronic health records. Automated algorithms identified limb outcomes used to build Cox proportional hazards regression models. Ankle-brachial indices and presence of poorly compressible arteries were electronically identified from digital data sets. Guideline-recommended management strategies within 6 months of diagnosis were also electronically retrieved, including therapy with statins, antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and smoking abstention. Main Outcomes and Measures: Ankle-brachial index (index ≤0.9 indicates PAD; <.05, severe PAD; and ≥1.40, poorly compressible arteries) and limb revascularization or amputation. Results: Of 1413 patients, 633 (44.8%) were women; mean (SD) age was 70.8 (13.3) years. A total of 283 patients (20.0%) had severe PAD (ankle-brachial indices <0.5) and 350 (24.8%) had poorly compressible arteries (ankle-brachial indices ≥1.4); 780 (55.2%) individuals with less than severe disease formed the reference group. Only 32 of 283 patients (11.3%) with severe disease and 68 of 350 patients (19.4%) with poorly compressible arteries were receiving 4 guideline-recommended management strategies. In the severe disease subgroup, the 1-year event rate for revascularization was 32.4% (90 events); in individuals with poorly compressible arteries, the 1-year amputation rate was 13.9% (47 events). In models adjusted for age, sex, and critical limb ischemia, poorly compressible arteries were associated with amputation (hazard ratio [HR], 3.12; 95% CI, 2.16-4.50; P < .001) but not revascularization (HR, 0.91; 95% CI, 0.69-1.20; P = .49). In contrast, severe disease was associated with revascularization (HR, 2.69; 95% CI, 2.15-3.37; P < .001) but not amputation (HR, 1.30; 95% CI, 0.82-2.07; P = .27). Conclusions and Relevance: Community-dwelling patients with severe PAD or poorly compressible arteries have high rates of revascularization or limb loss, respectively. Guideline-recommended management strategies for secondary risk prevention are underused in the community.

Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study.

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls ( p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle-brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

Clinical information extraction applications: A literature review.

BACKGROUND: With the rapid adoption of electronic health records (EHRs), it is desirable to harvest information and knowledge from EHRs to support automated systems at the point of care and to enable secondary use of EHRs for clinical and translational research. One critical component used to facilitate the secondary use of EHR data is the information extraction (IE) task, which automatically extracts and encodes clinical information from text. OBJECTIVES: In this literature review, we present a review of recent published research on clinical information extraction (IE) applications. METHODS: A literature search was conducted for articles published from January 2009 to September 2016 based on Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and ACM Digital Library. RESULTS: A total of 1917 publications were identified for title and abstract screening. Of these publications, 263 articles were selected and discussed in this review in terms of publication venues and data sources, clinical IE tools, methods, and applications in the areas of disease- and drug-related studies, and clinical workflow optimizations. CONCLUSIONS: Clinical IE has been used for a wide range of applications, however, there is a considerable gap between clinical studies using EHR data and studies using clinical IE. This study enabled us to gain a more concrete understanding of the gap and to provide potential solutions to bridge this gap.

Surveillance of Peripheral Arterial Disease Cases Using Natural Language Processing of Clinical Notes.

Peripheral arterial disease (PAD) is a chronic disease that affects millions of people worldwide and yet remains underdiagnosed and undertreated. Early detection is important, because PAD is strongly associated with an increased risk of mortality and morbidity. In this study, we built a PAD surveillance system using natural language processing (NLP) for early detection of PAD from narrative clinical notes. Our NLP algorithm had excellent positive predictive value (0.93) and identified 41% of PAD cases before the initial ankle-brachial index (ABI) test date while in 12% of cases the NLP algorithm detected PAD on the same date as the ABI (the gold standard for comparison). Hence, our system ascertains PAD patients in a timely and accurate manner. In conclusion, our PAD surveillance NLP algorithm has the potential for translation to clinical practice for use in reminding clinicians to order ABI tests in patients with suspected PAD and to reinforce the implementation of guideline recommended risk modification strategies in patients diagnosed with PAD.

Mining peripheral arterial disease cases from narrative clinical notes using natural language processing.

OBJECTIVE: Lower extremity peripheral arterial disease (PAD) is highly prevalent and affects millions of individuals worldwide. We developed a natural language processing (NLP) system for automated ascertainment of PAD cases from clinical narrative notes and compared the performance of the NLP algorithm with billing code algorithms, using ankle-brachial index test results as the gold standard. METHODS: We compared the performance of the NLP algorithm to (1) results of gold standard ankle-brachial index; (2) previously validated algorithms based on relevant International Classification of Diseases, Ninth Revision diagnostic codes (simple model); and (3) a combination of International Classification of Diseases, Ninth Revision codes with procedural codes (full model). A dataset of 1569 patients with PAD and controls was randomly divided into training (n = 935) and testing (n = 634) subsets. RESULTS: We iteratively refined the NLP algorithm in the training set including narrative note sections, note types, and service types, to maximize its accuracy. In the testing dataset, when compared with both simple and full models, the NLP algorithm had better accuracy (NLP, 91.8%; full model, 81.8%; simple model, 83%; P < .001), positive predictive value (NLP, 92.9%; full model, 74.3%; simple model, 79.9%; P < .001), and specificity (NLP, 92.5%; full model, 64.2%; simple model, 75.9%; P < .001). CONCLUSIONS: A knowledge-driven NLP algorithm for automatic ascertainment of PAD cases from clinical notes had greater accuracy than billing code algorithms. Our findings highlight the potential of NLP tools for rapid and efficient ascertainment of PAD cases from electronic health records to facilitate clinical investigation and eventually improve care by clinical decision support.