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After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms.Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years.Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p 0.001).Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported.We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis.Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years.There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.Level IV, therapeutic study.

India is home to 1.3 billion people who are exposed to some of the highest levels of ambient air pollution in the world. In addition, India is one of the fastest-growing carbon-emitting countries. Here, we assess how two strategies to reuse waste-heat from coal-fired power plants and other large sources would impact PM

To determine the glycaemic control and associated factors among patients with type-2 diabetes mellitus on tiered metformin monotherapy over one-year.Adult Asian patients on metformin monotherapy with tiered dosage up-titration (low 500 mg/day; medium 500-1000 mg/day and high ≥ 1000 mg/day) are divided into four sub-cohorts based on their baseline HbA1c 7%(CAmong 5503 eligible patients (mean age = 64.9 years, 45.6% males and 74.6% Chinese), the HbA1c absolute reduction after the up-titration at three months are 0%, 0.4%-0.6%, 0.8%-1.2% and 2.0%-2.1% for CThe results show that the baseline HbA1c and tiered metformin dosage up-titration are associated with disproportionate HbA1c reduction, time to glycaemic control and time from glycaemic control to failure.

Background Clinical trials have demonstrated that initiating oral anti-diabetic drugs (OADs) significantly reduce glycated hemoglobin (HbA1c) levels. However, variability in lifestyle modifications and OAD adherence impact on their actual effect on glycemic control. Furthermore, evidence on dose adjustments and discontinuation of OAD on HbA1c is lacking. This study aims to use real-world data to determine the effect of OAD initiation, up-titration, down-titration, and discontinuation on HbA1c levels, among Asian patients managed in primary care. Methods A retrospective cohort study over a 5-year period, from Jan 2015 to Dec 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of type 2 diabetes mellitus (T2DM) managed by a network of primary care clinics in Singapore. Nine OADs from five different classes (biguanides, sulphonyurea, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 [SGLT-2] inhibitors, and alpha-glucosidase inhibitors) were evaluated. Patients were grouped into “No OAD”, “Non-titrators,” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the various OAD titrations were identified. Subsequently, a descriptive analysis of HbA1c values before and after each titration was performed to compute a mean difference for each unique titration identified. Results Among the cohort of 57,910 patients, 43,338 of them had at least one OAD titration, with a total of 76,990 pairs of HbA1c values associated with an OAD titration. There were a total of 206 unique OAD titrations. Overall, initiation of OADs resulted in a reduction of HbA1c by 3 to 12 mmol/mol (0.3 to 1.1%), respectively. These results were slightly lower than those reported in clinical trials of 6 to 14 mmol/mol (0.5 to 1.25%). The change of HbA1c levels due to up-titration, down-titration, and discontinuation were −1 to −8 mmol/mol (−0.1 to −0.7%), +1 to 7 mmol/mol (+0.1 to +0.6%), and +2 to 11 mmol/mol (+0.2 to +1.0%), respectively. The HbA1c lowering effect of initiating newer OADs, namely DPP-4 inhibitors and SGLT-2 inhibitors was 8 to 11 mmol/mol (0.7 to 0.9%) and 7 to 11 mmol/mol (0.6 to 1.0%), respectively. Conclusion The real-world data on Asians with T2DM in this study show that the magnitudes of OAD initiation and dose titration are marginally lower than the results from clinical trials. During shared decision-making in selecting treatment options, the results enable physicians to communicate realistic expectation of the effect of oral medications on the glycemic control of their patients in primary care.

Early drain removal when postoperative day (POD) one drain fluid amylase (DFA) was ≤5000 U/L reduced complications in a previous randomized controlled trial. We hypothesized that most surgeons continue to remove drains late and this is associated with inferior outcomes.We assessed the practice of surgeons in a prospectively maintained pancreas surgery registry to determine the association between timing of drain removal with demographics, comorbidities, and complications. We selected patients with POD1 DFA ≤5000 U/L and excluded those without drains, and subjects without data on POD1 DFA or timing of drain removal. Early drain removal was defined as ≤ POD5.Two hundred and forty four patients met inclusion criteria. Only 90 (37%) had drains removed early. Estimated blood loss was greater in the late removal group (190 mL versus 100 mL, P = 0.005) and pathological findings associated with soft gland texture were more frequent (97 [63%] versus 35 [39%], P 0.0001). Patients in the late drain removal group had more complications (84 [55%] versus 30 [33%], P = 0.001) including pancreatic fistula (55 [36%] versus 4 [4%], P 0.0001), delayed gastric emptying (27 [18%] versus 3 [3%], P = 0.002), and longer length of stay (7 d versus 5 d, P 0.0001). In subset analysis for procedure type, complications and pancreatic fistula remained significant for both pancreatoduodenectomy and distal pancreatectomy.Despite level one data suggesting improved outcomes with early removal when POD1 DFA is ≤ 5000 U/L, experienced pancreas surgeons more frequently removed drains late. This practice was associated with known risk factors (estimated blood loss, soft pancreas) and may be associated with inferior outcomes suggesting potential for improvement.

Background Clinical trials have demonstrated that either initiating or up-titrating a statin dose substantially reduce Low-Density Lipoprotein-Cholesterol (LDL-C) levels. However, statin adherence in actual practice tends to be suboptimal, leading to diminished effectiveness. This study aims to use real-world data to determine the effect on LDL-C levels and LDL-C goal attainment rates, when selected statins are titrated in Asian patients. Methods A retrospective cohort study over a 5-year period, from April 2014 to March 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of Dyslipidaemia in a primary care clinic in Singapore. The statins were classified into low-intensity (LI), moderate-intensity (MI) and high-intensity (HI) groups according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Patients were grouped into “No statin”, “Non-titrators” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the mean percentage change in LDL-C and absolute change in LDL-C goal attainment rates were computed for each permutation of statin intensity titration. Results Among the cohort of 11,499 patients, with a total of 266,762 visits, there were 1962 pairs of LDL-C values associated with a statin titration. Initiation of LI, MI and HI statin resulted in a lowering of LDL-C by 21.6% (95%CI = 18.9–24.3%), 28.9% (95%CI = 25.0–32.7%) and 25.2% (95%CI = 12.8–37.7%) respectively. These were comparatively lower than results from clinical trials (30 to 63%). The change of LDL-C levels due to up-titration, down-titration, and discontinuation were − 12.4% to − 28.9%, + 13.2% to + 24.6%, and + 18.1% to + 32.1% respectively. The improvement in LDL-C goal attainment ranged from 26.5% to 47.1% when statin intensity was up-titrated. Conclusion In this study based on real-world data of Asian patients in primary care, it was shown that although statin titration substantially affected LDL-C levels and LDL-C goal attainment rates, the magnitude was lower than results reported from clinical trials. These results should be taken into consideration and provide further insight to clinicians when making statin adjustment recommendations in order to achieve LDL-C targets in clinical practice, particularly for Asian populations.

Pancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose.Patients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival.Of the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P0.05). New IDDM was also associated with a decreased cancer-specific survival.Preoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively.

BackgroundEarly warning scores (EWS) have been developed as clinical prognostication tools to identify acutely deteriorating patients. In the past few years, there has been a proliferation of studies that describe the development and validation of novel machine learning-based EWS. Systematic reviews of published studies which focus on evaluating performance of both well-established and novel EWS have shown conflicting conclusions. A possible reason is the heterogeneity in validation methods applied. In this review, we aim to examine the methodologies and metrics used in studies which perform EWS validation.MethodsA systematic review of all eligible studies from the MEDLINE database and other sources, was performed. Studies were eligible if they performed validation on at least one EWS and reported associations between EWS scores and inpatient mortality, intensive care unit (ICU) transfers, or cardiac arrest (CA) of adults. Two reviewers independently did a full-text review and performed data abstraction by using standardized data-worksheet based on the TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist. Meta-analysis was not performed due to heterogeneity.ResultsThe key differences in validation methodologies identified were (1) validation dataset used, (2) outcomes of interest, (3) case definition, time of EWS use and aggregation methods, and (4) handling of missing values. In terms of case definition, among the 48 eligible studies, 34 used the patient episode case definition while 12 used the observation set case definition, and 2 did the validation using both case definitions. Of those that used the patient episode case definition, 18 studies validated the EWS at a single point of time, mostly using the first recorded observation. The review also found more than 10 different performance metrics reported among the studies.ConclusionsMethodologies and performance metrics used in studies performing validation on EWS were heterogeneous hence making it difficult to interpret and compare EWS performance. Standardizing EWS validation methodology and reporting can potentially address this issue.

Background Blockchain technology has the potential to enable more secure, transparent, and equitable data management. In the health care domain, it has been applied most frequently to electronic health records. In addition to securely managing data, blockchain has significant advantages in distributing data access, control, and ownership to end users. Due to this attribute, among others, the use of blockchain to power personal health records (PHRs) is especially appealing. Objective This review aims to examine the current landscape, design choices, limitations, and future directions of blockchain-based PHRs. Methods Adopting the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, a cross-disciplinary systematic review was performed in July 2020 on all eligible articles, including gray literature, from the following 8 databases: ACM, IEEE Xplore, MEDLINE, ScienceDirect, Scopus, SpringerLink, Web of Science, and Google Scholar. Three reviewers independently performed a full-text review and data abstraction using a standardized data collection form. Results A total of 58 articles met the inclusion criteria. In the review, we found that the blockchain PHR space has matured over the past 5 years, from purely conceptual ideas initially to an increasing trend of publications describing prototypes and even implementations. Although the eventual application of blockchain in PHRs is intended for the health care industry, the majority of the articles were found in engineering or computer science publications. Among the blockchain PHRs described, permissioned blockchains and off-chain storage were the most common design choices. Although 18 articles described a tethered blockchain PHR, all of them were at the conceptual stage. Conclusions This review revealed that although research interest in blockchain PHRs is increasing and that the space is maturing, this technology is still largely in the conceptual stage. Being the first systematic review on blockchain PHRs, this review should serve as a basis for future reviews to track the development of the space.

A circumcising incision to deglove the penis for penile prosthesis (PP) implantation can increase the risk of ischemic injury to the glans penis. In order to avoid vascular complications, we describe a novel technique utilizing a ventral incision to perform the PP implantation and a double-dorsal patch graft, or “sliding technique” (ST), in patients with severe Peyronie's disease (PD). Three patients with severe PD and erectile dysfunction at our institution underwent ST and PP implantation through a ventral incision. This new approach was not only successful in facilitating the ST and PP implantation in these patients but also allowed for adequate exposure of the penile shaft with no reported loss of sensation. We also conducted a review of current literature regarding the approaches for PD. While ischemic complications of PP implantation and ST are rare, there are reports of ischemic injury in patients undergoing a circumcising incision. The combination of a circumcising incision and a patient's underlying peripheral artery disease potentially raises a patient's risk of this rare complication. Our innovative ventral incision provides an alternative method for PP implantation and ST in order to avoid ischemia of the penis, while still allowing for adequate exposure.

The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications.The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported.Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy.A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores.This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

The amyloid β peptide (Aβ) is a key player in the etiology of Alzheimer disease (AD), yet a systematic investigation of its molecular interactions has not been reported. Here we identified by quantitative mass spectrometry proteins in human brain extract that bind to oligomeric Aβ1-42 (oAβ1-42) and/or monomeric Aβ1-42 (mAβ1-42) baits. Remarkably, the cyclic neuroendocrine peptide somatostatin-14 (SST14) was observed to be the most selectively enriched oAβ1-42 binder. The binding interface comprises a central tryptophan within SST14 and the N-terminus of Aβ1-42. The presence of SST14 inhibited Aβ aggregation and masked the ability of several antibodies to detect Aβ. Notably, Aβ1-42, but not Aβ1-40, formed in the presence of SST14 oligomeric assemblies of 50 to 60 kDa that were visualized by gel electrophoresis, nanoparticle tracking analysis and electron microscopy. These findings may be relevant for Aβ-directed diagnostics and may signify a role of SST14 in the etiology of AD. DOI: http://dx.doi.org/10.7554/eLife.28401.001, eLife digest Treating Alzheimer’s disease and related dementias is one of the major challenges currently facing healthcare providers worldwide. A hallmark of the disease is the formation of large deposits of a specific molecule, known as amyloid beta (Aβ), in the brain. However, more and more research suggests that smaller and particularly toxic amyloid beta clumps – often referred to as oligomeric Aβ – appear as an early sign of Alzheimer’s disease. To understand how the formation of these smaller amyloid beta clumps triggers other aspects of the disease, it is important to identify molecules in the human brain that oligomeric Aβ binds to. To this end, Wang et al. attached amyloid beta or oligomeric Aβ molecules to microscopically small beads. The beads were then exposed to human brain extracts in a test tube, which allowed molecules in the extracts to bind to the amyloid beta or oligomeric Aβ. The samples were then spun at high speed, meaning that the beads and any other molecules bound to them sunk and formed pellets at the bottom of the tubes. Each pellet was then analyzed to see which molecules it contained. The experiments identified more than a hundred human brain proteins that can bind to amyloid beta. One of them, known as somatostatin, selectively binds to oligomeric Aβ. Wang et al. were able to determine the structural features of somatostatin that control this binding. Finally, in further experiments performed in test tubes, Wang et al. noticed that smaller oligomeric Aβ clumps were more likely to form than larger amyloid beta deposits when somatostatin was present. This could signify a previously unrecognized role of somatostatin in the development of Alzheimer’s disease. Further studies are now needed to confirm whether the presence of somatostatin in the brain favors the formation of smaller, toxic oligomeric Aβ clumps over large innocuous amyloid beta deposits. If so, new treatments could be developed that aim to reduce oligomeric Aβ levels in the brain by preventing somatostatin from interacting with amyloid beta molecules. Wang et al. also suggest that somatostatin could be used in diagnostic tests to detect abnormal levels of oligomeric Aβ in the brain or body fluids of people who have Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.28401.002

Study design A retrospective case control analysis of 48 cases of postoperative infection following spinal procedures. Objectives Spinal procedures that became infected after surgery were analyzed to identify the significance of preoperative and intraoperative risk factors. Characterization of the nature and timing of the infections was also performed. Summary of background data The rate of postoperative infection following spinal surgery varies widely depending on the nature of the procedure and the patient's diagnosis. Preoperative comorbidities and risk factors also influence the likelihood of infection. Methods A review of 1629 procedures performed on 1095 patients revealed that a postoperative infection developed in 48 patients (4.4%). Data regarding preoperative and intraoperative risk factors were gathered from patient charts for these and a randomly selected control group of 95 uninfected patients. For analysis, these patient groups were further divided into adult and pediatric subgroups, with an age cutoff of 18 years. Preoperative risk factors reviewed included smoking, diabetes, previous surgery, previous infection, steroid use, body mass index, and alcohol abuse. Intraoperative factors reviewed included staging of procedures, estimated blood loss, operating time, and use of allograft or instrumentation. Results The majority of infections occurred during the early postoperative period (less than 3 months). Age >60 years, smoking, diabetes, previous surgical infection, increased body mass index, and alcohol abuse were statistically significant preoperative risk factors. The most likely procedure to be complicated by an infection was a combined anterior/posterior spinal fusion performed in a staged manner under separate anesthesia. Infections were primarily monomicrobial, although 5 patients had more than 4 organisms identified. The most common organism cultured from the wounds was Staphylococcus aureus. All patients were treated with surgical irrigation and debridement, and appropriate antibiotics to treat the cultured organism. Conclusions Aggressive treatment of patients undergoing complex or prolonged spinal procedures is essential to prevent and treat infections. Understanding a patient's preoperative risk factors may help the physician to optimize a patient's preoperative condition. Additionally, awareness of critical intraoperative parameters will help to optimize surgical treatment. It may be appropriate to increase the duration of prophylactic antibiotics or implement other measures to decrease the incidence of infection for high risk patients.