Development of a personalized diagnostic model for kidney stone disease tailored to acute care by integrating large clinical, demographics and laboratory data: the diagnostic acute care algorithm - kidney stones (DACA-KS).

BACKGROUND: Kidney stone (KS) disease has high, increasing prevalence in the United States and poses a massive economic burden. Diagnostics algorithms of KS only use a few variables with a limited sensitivity and specificity. In this study, we tested a big data approach to infer and validate a 'multi-domain' personalized diagnostic acute care algorithm for KS (DACA-KS), merging demographic, vital signs, clinical, and laboratory information. METHODS: We utilized a large, single-center database of patients admitted to acute care units in a large tertiary care hospital. Patients diagnosed with KS were compared to groups of patients with acute abdominal/flank/groin pain, genitourinary diseases, and other conditions. We analyzed multiple information domains (several thousands of variables) using a collection of statistical and machine learning models with feature selectors. We compared sensitivity, specificity and area under the receiver operating characteristic (AUROC) of our approach with the STONE score, using cross-validation. RESULTS: Thirty eight thousand five hundred and ninety-seven distinct adult patients were admitted to critical care between 2001 and 2012, of which 217 were diagnosed with KS, and 7446 with acute pain (non-KS). The multi-domain approach using logistic regression yielded an AUROC of 0.86 and a sensitivity/specificity of 0.81/0.82 in cross-validation. Increase in performance was obtained by fitting a super-learner, at the price of lower interpretability. We discussed in detail comorbidity and lab marker variables independently associated with KS (e.g. blood chloride, candidiasis, sleep disorders). CONCLUSIONS: Although external validation is warranted, DACA-KS could be integrated into electronic health systems; the algorithm has the potential used as an effective tool to help nurses and healthcare personnel during triage or clinicians making a diagnosis, streamlining patients' management in acute care.

Provision of Kidney Disease Education Service Is Associated with Improved Vascular Access Outcomes among US Incident Hemodialysis Patients.

Background: Pre-ESKD Kidney Disease Education (KDE) has been shown to improve multiple CKD outcomes, but its effect on vascular access outcomes is not well studied. In 2010, Medicare launched KDE reimbursements policy for patients with advanced CKD. Methods: In this retrospective USRDS analysis, we identified all adult patients on incident hemodialysis with ≥6 months of pre-ESKD Medicare coverage during the first 5 years of CMS-KDE policy and divided them into CMS-KDE services recipients (KDE cohort) and nonrecipients (non-KDE cohort). The primary outcome was incident arteriovenous fistula (AVF) and the composite of incident AVF or arteriovenous graft (AVG) utilization. Secondary outcomes were central venous catheter (CVC) with maturing AVF/AVG and pure CVC utilizations. Step-wise multivariate analyses were performed in four progressive models (model 1, KDE alone; model 2, multivariate model encompassing model 1 with sociodemographics; model 3, model 2 with comorbidity and functional status; and model 4, model 3 with pre-ESKD nephrology care). Results: Of the 211,990 qualifying patients on incident hemodialysis during the study period, 2887 (1%) received KDE services before dialysis initiation. The rates of incident AVF and composite AVF/AVG were more than double (30% and 35%, respectively, compared with 14% and 17%), and pure catheter use about a third lower (40% compared with 65%) in the KDE cohort compared with the non-KDE cohort. The maximally adjusted odds ratios in model 4 for study outcomes were incident AVF use, 1.78, 99% confidence interval, 1.55 to 2.05; incident AVF/AVG use, 1.78, 99% confidence interval, 1.56 to 2.03; incident CVC with maturing AVF/AVG, 1.69, 99% confidence interval, 1.44 to 1.97; and pure CVC without any AVF/AVG, 0.51, 99% confidence interval, 0.45 to 0.58. The benefits of the KDE service were maintained even after accounting for the presence, duration, and facility of ESKD care. Conclusion: The occurrence of pre-ESRD KDE service is associated with significantly improved incident vascular access outcomes. Targeted studies are needed to examine the effect of KDE on patient engagement and self-efficacy as a cause for improvement in vascular access outcomes.

Gene therapy for chronic neuropathic pain: how does it work and where do we stand today?

OBJECTIVES: Chronic neuropathic pain has been an enigma to physicians and researchers for decades. A better understanding of its pathophysiology has given us more insight into its various mechanisms and possible treatment options. We now have an understanding of the role of various ionic channels, biologically active molecules involved in pain, and also the intricate pain pathways where possible interventions might lead to substantial pain relief. The recent research on laboratory animals using virus-based vectors for gene transfer at targeted sites is very promising and may lead to additional human clinical trials. However, one needs to be aware that this "novel" approach is still in its infancy and that many of its details need to be further elucidated. The purpose of this article is to thoroughly review the current available literature and analyze the deficiencies in our current knowledge. DESIGN: Literature review. METHODS: After an extensive online literature search, a total of 133 articles were selected to synthesize a comprehensive review about chronic neuropathic pain and gene therapy in order to understand the concepts and mechanisms. RESULTS: Most of the studies have shown benefits of gene therapy in animal models, and recently, phase 1 human trials using herpes simplex virus vector have started for intractable cancer pain. CONCLUSION: Although animal data have shown safety and efficacy, and initial human trials have been promising, additional studies in humans are required to more completely understand the actual benefits and risks of using gene therapy for the treatment of chronic neuropathic pain.

Unusual cause of persistent dyspnea in a patient with nephrotic syndrome: dapsone-induced methemoglobinemia.

Acquired methemoglobinemia is a rare, but important cause of tissue hypoxemia, which often results from commonly prescribed medications. We report a case of an 83-year-old female with stage III chronic kidney disease, who was started on high-dose prednisone for nephrotic syndrome and dapsone for pneumocystis jirovecii pneumonia prophylaxis. A week after initiation of dapsone, this patient presented with shortness of breath, and an oxygen saturation gap while on supplemental O2 via nasal cannula, with no obvious cardiopulmonary cause. Methemoglobin level was elevated on arterial blood gas. Our patient was treated with IV methylene blue. Dapsone was determined to be the culprit and immediately discontinued. Patient responded with a rapid decrease in methemoglobin levels and resolution of symptoms. This case report highlights the importance of maintaining a high index of suspicion and careful review of medication history for prompt and successful management of methemoglobin poisoning, as not all patients present with classical signs of methemoglobinemia such as cyanosis and/ or dark red blood.

Anterolateral intervertebral disc herniation presenting as visceral pain in a patient with renal keratinising desquamative squamous metaplasia.

We report the case of a 70-year-old man who presented to the clinic with back pain and presumed chronic kidney pain from renal keratinising desquamative squamous metaplasia, in which he would intermittently pass keratin plugs in urine. The pain had a visceral-sounding component that was inconsistent with renal colic. MRI of the spine revealed anterolateral disc bulges, which were likely irritating the anterolateral sympathetic nerves of the intervertebral disc, mimicking visceral pain. Transforaminal epidural steroid injection (TFESI) was performed at the levels of the disc bulges. He had no pain during passage of keratin plugs for 6.5 months after the TFESI which could be attributed to the expected duration of symptoms relief after a properly done TFESI.

Pro Re Nata Antihypertensive Medications and Adverse Outcomes in Hospitalized Patients: A Propensity-Matched Cohort Study.

[Figure: see text].

Utilization of CMS pre-ESRD Kidney Disease Education services and its associations with the home dialysis therapies.

BACKGROUND: Kidney Disease Education (KDE) has been shown to improve informed dialysis selection and home dialysis use, two long-held but underachieved goals of US nephrology community. In 2010, the Center for Medicare and Medicaid Services launched a policy of KDE reimbursements for all Medicare beneficiaries with advanced chronic kidney disease. However, the incorporation of KDE service in real-world practice and its association with the home dialysis utilization has not been examined. METHODS: Using the 2016 US Renal Data System linked to end-stage renal disease (ESRD) and pre-ESRD Medicare claim data, we identified all adult incident ESRD patients with active Medicare benefits at their first-ever dialysis during the study period (1 January 2010 to 31 December 2014). From these, we identified those who had at least one KDE service code before their dialysis initiation (KDE cohort) and compared them to a parsimoniously matched non-KDE control cohort in 1:4 proportions for age, gender, ESRD network, and the year of dialysis initiation. The primary outcome was home dialysis use at dialysis initiation, and secondary outcomes were home dialysis use at day 90 and anytime through the course of ESRD. RESULTS: Of the 369,968 qualifying incident ESRD Medicare beneficiaries with their first-ever dialysis during the study period, 3469 (0.9%) received KDE services before dialysis initiation. African American race, Hispanic ethnicity, and the presence of congestive heart failure and hypoalbuminemia were associated with significantly lower odds of receiving KDE services. Multivariate analyses showed that KDE recipients had twice the odds of initiating dialysis with home modalities (15.0% vs. 6.9%; adjusted odds ratio (aOR):95% confidence interval (CI) 2.0:1.7-2.4) and had significantly higher odds using home dialysis throughout the course of ESRD (home dialysis use at day 90 (17.6% vs. 9.9%, aOR:CI 1.7:1.4-1.9) and cumulatively (24.7% vs. 15.1%, aOR:CI 1.7:1.5-1.9)). CONCLUSIONS: Utilization of pre-ESRD KDE services is associated with significantly greater home dialysis utilization in the incident ESRD Medicare beneficiaries. The very low rates of utilization of these services suggest the need for focused systemic evaluations to identify and address the barriers and facilitators of this important patient-centered endeavor.

Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis.

Importance: Prolonged opioid use after surgery may be associated with opioid dependency and increased health care use. However, published studies have reported varying estimates of the magnitude of prolonged opioid use and risk factors associated with the transition of patients to long-term opioid use. Objectives: To evaluate the rate and characteristics of patient-level risk factors associated with increased risk of prolonged use of opioids after surgery. Data Sources: For this systematic review and meta-analysis, a search of MEDLINE, Embase, and Google Scholar from inception to August 30, 2017, was performed, with an updated search performed on June 30, 2019. Key words may include opioid analgesics, general surgery, surgical procedures, persistent opioid use, and postoperative pain. Study Selection: Of 7534 articles reviewed, 33 studies were included. Studies were included if they involved participants 18 years or older, evaluated opioid use 3 or more months after surgery, and reported the rate and adjusted risk factors associated with prolonged opioid use after surgery. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two reviewers independently assessed and extracted the relevant data. Main Outcomes and Measures: The weighted pooled rate and odds ratios (ORs) of risk factors were calculated using the random-effects model. Results: The 33 studies included 1 922 743 individuals, with 1 854 006 (96.4%) from the US. In studies with available sex and age information, participants were mostly female (1 031 399; 82.7%) and had a mean (SD) age of 59.3 (12.8) years. The pooled rate of prolonged opioid use after surgery was 6.7% (95% CI, 4.5%-9.8%) but decreased to 1.2% (95% CI, 0.4%-3.9%) in restricted analyses involving only opioid-naive participants at baseline. The risk factors with the strongest associations with prolonged opioid use included preoperative use of opioids (OR, 5.32; 95% CI, 2.94-9.64) or illicit cocaine (OR, 4.34; 95% CI, 1.50-12.58) and a preoperative diagnosis of back pain (OR, 2.05; 95% CI, 1.63-2.58). No significant differences were observed with various study-level factors, including a comparison of major vs minor surgical procedures (pooled rate: 7.0%; 95% CI, 4.9%-9.9% vs 11.1%; 95% CI, 6.0%-19.4%; P = .20). Across all of our analyses, there was substantial variability because of heterogeneity instead of sampling error. Conclusions and Relevance: The findings suggest that prolonged opioid use after surgery may be a substantial burden to public health. It appears that strategies, such as proactively screening for at-risk individuals, should be prioritized.

Unusual complication of an Alaskan cruise: thinking outside the box.

A 69-year-old man with a medical history of hypertension and diabetes presented with altered mental status once he returned from a 14-day Alaskan cruise. An extensive workup for stroke was negative. His physical examination was normal without any focal motor deficits, but he had developed memory loss and paresthesia. He admitted to eating a lot of fish when he was in Alaska. The whole-blood mercury level was found to be elevated. He was managed conservatively and his symptoms resolved completely in a few days. This led to a diagnosis of organic mercury toxicity.

Think before you leap: cutaneous hypersensitivity to polytetrafluoroethylene arteriovenous graft masquerading as infection.

Polytetrafluoroethylene (PTFE) graft is a synthetic graft commonly used in chronic haemodialysis patients. Expected complications of synthetic grafts include infection, thrombosis, oedema and pain. PTFE is a non-textile graft that is chemically inert, electronegative and hydrophobic. Due to their chemical properties, PTFE grafts have lower risks of these adversities. We present a patient with a rare case of cutaneous hypersensitivity to a PTFE graft.

Erroneously High Lactate: A Guide to Diagnosing Ethylene Glycol Poisoning.

A high lactic acid level in critically ill patients is a marker of poor prognosis. However, lactic acidosis in ethylene glycol (EG) poisoning should be interpreted cautiously as analytical interference is observed with EG metabolites.

Opioid Safety and Concomitant Benzodiazepine Use in End-Stage Renal Disease Patients.

Background: Opioid use is common in end-stage renal disease (ESRD) patients. However, safety of individual opioids and concomitant benzodiazepine use has not been studied. Objective: To study the epidemiology of opioid and concomitant benzodiazepine use in ESRD population. To study the clinical safety profile of individual opioids in patients on hemodialysis. Design: Retrospective analysis of the U.S. Renal Data System. A comprehensive review of the current literature was performed to update currently used opioid safety classification. Participants: ESRD patients ≥18 years on hemodialysis who were enrolled in Medicare A and B and Part D between 2006 and 2012, excluding those with malignancy. Main Measures: Hospital admission with diagnosis of prescription opioid overdose within 30, 60, and 90 days of prescription; death due to opioid overdose. Results: Annually, the percentage of patients prescribed any opioid was 52.2%. Overall trend has been increasing except for a small dip in 2011, despite which the admissions due to opioid overdose have been rising. 30% of those who got a prescription for opioids also got a benzodiazepine prescription. 56.5% of these patients received both prescriptions within a week of each other. Benzodiazepine use increased the odds of being on opioids by 3.27 (CI 3.21-3.32) and increased the odds of hospitalization by 50%. Opioids considered safe such as fentanyl and methadone were associated with 3 and 6 folds higher odds of hospitalization within 30 days of prescription. Hydrocodone had the lowest odds ratio (1.9, CI 1.8-2.0). Conclusions: Concurrent benzodiazepine use is common and associated with higher risk of hospitalization due to opioid overdose. Possible opioid-associated hospital admission rate is 4-5 times bigger in ESRD population than general population. Current safety classification of opioids in these patients is misleading, and even drugs considered safe based on pharmacokinetic data are associated with moderate to very high risk of hospitalization. We propose a risk-stratified classification of opioids and suggest starting to use them in all ESRD patients.

Fulminant eye infection in a patient with nephrotic syndrome.

Endophthalmitis is a bacterial or fungal infection inside the eye, involving the vitreous and/or aqueous humors. High index of suspicion is required for this condition in immunocompromised patients with ocular complaints as it can worsen rapidly and lead to permanent loss of vision.

Spontaneous renal artery dissection masquerading as urinary tract infection.

Spontaneous renal artery dissection is a rare clinical entity, and symptoms vary from non-specific abdominal pain to life-threatening hypertension. A 44-year-old woman with no significant medical history initially presented with symptoms suggestive of urinary tract infection which did not respond to antibiotic therapy. Imaging revealed right renal infarction resulting from focal spontaneous renal artery dissection, which was managed conservatively. CT angiography is the preferred imaging modality for the diagnosis of this condition. Treatment options include medical management of hypertension with or without anticoagulation, endovascular intervention and surgical revascularisation depending on the presentation and the extent of the vascular and renal parenchymal involvement. This case emphasises the need to have high index of suspicion for uncommon diagnoses in patients who present with common symptoms but do not respond to empiric therapy.

Hypokalemia: A potentially life-threatening complication of tenofovir therapy.

Tenofovir is a nucleotide analog reverse transcriptase inhibitor approved for the treatment of HIV and hepatitis B infections. It is widely prescribed and an integral part of the recommended regimens for the treatment of HIV infection in antiretroviral-naive patients. Tenofovir is implicated in renal proximal tubular dysfunction, which can be associated with Fanconi syndrome and hypokalemia. When the hypokalemia is severe, it can lead to life-threatening complications. We describe the case of a 59-year-old woman who suffered a cardiac arrest secondary to severe hypokalemia from tenofovir use.

Perioperative Acute Kidney Injury: Risk Factors and Predictive Strategies.

Acute kidney injury (AKI) is a common complication in surgical patients and is associated with increases in mortality, an increased risk for chronic kidney disease and hemodialysis after discharge, and increased cost. Better understanding of the risk factors that contribute to perioperative AKI has led to improved AKI prediction and will eventually lead to improved prevention of AKI, mitigation of injury when AKI occurs, and enhanced recovery in patients who sustain AKI. The development of advanced clinical prediction scores for AKI, new imaging techniques, and novel biomarkers for early detection of AKI provides new tools toward these ends.