Association of Thiazide Diuretics With Diabetes Progression, Kidney Disease Progression, Cardiovascular Outcomes, and Death Among Patients With Diabetes Who Initiate Statins.

Statins have been associated with diabetes mellitus (DM) progression but their cardiovascular benefit in patients with DM outweigh the harm. However, the effects of concurrent use of other medications that similarly increase blood glucose level, such as thiazide diuretics, are not well studied. This study aimed to evaluate the association of concurrent use of thiazide diuretics and statins on DM progression, cardiovascular and renal outcomes, and death in patients with DM. This is a retrospective cohort study of Veterans with DM who initiated statins between 2003 and 2015. The cohort comprised thiazide users (concomitantly used thiazides and statins for ≥6 months) and active comparators (concomitantly used calciun channel blockers [CCB] but not thiazides and statins for ≥6 months). We excluded patients who were <18 years old, with chronic kidney disease stage 4 or worse, or used loop diuretics. We propensity-score-matched comparison groups on 99 baseline characteristics including demographics, healthcare utilization, co-morbidities, cardiovascular and co-morbidity scores, vital signs, laboratory data, and medication class usage. Outcomes were: (1) DM progression (new insulin initiation, increase in the number of glucose-lowering medication classes, and hyperglycemic episodes); (2) kidney disease progression (doubling of serum creatinine, incidence of chronic kidney disease stage 5, initiation of renal replacement therapy, and incidence of diabetic nephropathy); (3) cardiovascular outcomes (acute myocardial infarction, stroke, cardiac arrest); and (4) total mortality. From 297,967 statin users (228,509 Thiazide-statin users and 69,458 active comparators), we successfully matched 67,614 pairs. In comparison to active comparators, thiazide-statin users had increased risk of DM progression (65.6% in CCB group vs 68.1% in thiazide group; odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.09 to 1.15), decreased risk of kidney progression (16.9% in CCB group vs 16.5 in thiazide group; OR: 0.97, 95% CI: 0.94 to 0.99), decreased risk of cardiovascular outcomes (15.7% in CCB group vs 14.6% in thiazide group; OR: 0.92, 95% CI: 0.89 to 0.95), and similar risk of total mortality (19.7% in each group; OR: 1.00, 95% CI: 0.98 to 1.03). This study attempted to answer an important clinical question whether thiazide diuretics should be discontinued or substituted upon statin initiation. Our results showed that concurrent use of statin and thiazides in patients with DM was associated with DM progression but with less kidney progression and cardiovascular outcomes and no difference in mortality. Clinicians should closely monitor DM control when thiazides and statins are used concurrently.

A Fatal Case of Lisinopril-Induced Acute Necrotizing Pancreatitis.

Angiotensin-converting enzyme inhibitors (ACE-I), such as lisinopril, are used as first-line therapy in the treatment of hypertension, heart failure with reduced ejection fraction, and proteinuric chronic kidney disease due to their beneficial effects on reducing morbidity and mortality. Commonly cited adverse effects of lisinopril include hyperkalemia, acute kidney injury, and angioedema, and while uncommon, there have been reports of lisinopril-induced necrotizing pancreatitis in the literature. The true incidence of drug-induced pancreatitis is unknown since establishing a causal relationship between medication's adverse effects and disease occurrence is difficult; however, there are validated tools such as the Adverse Drug Reaction Probability Scale that can aid in determining causality. Here, we present a case of a 63-year-old man with a history of hypertension who was being treated with lisinopril for eight months and developed a fatal case of lisinopril-induced severe necrotizing pancreatitis.

Significance of Chronic Kidney Disease on Morbidity and Mortality in Hospitalized Patients With COVID-19.

Background: Patients with comorbid illnesses are at risk for worse outcomes with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19). Our research examined patients with chronic kidney disease (CKD) to establish whether it remains an independent risk factor for mortality and morbidity in patients with COVID-19. Methods: We conducted a retrospective cohort study using an electronic patient database in 2020. An observational dataset from 149 hospitals comprising a United States-based health system (HCA Healthcare) was analyzed. Hospitalized patients (N=11 086), aged 18 and above, with a COVID-19 polymerase chain reaction positive result between January 1, 2020, and September 1, 2020, were included in the initial data set.Primary outcomes were in-hospital death or discharge to hospice in patients with COVID-19. Secondary outcomes were individual components of the primary outcome including intensive care unit (ICU) admission, ventilator dependency, development of acute kidney injury (AKI), and in-hospital death. Baseline patient characteristics were recorded, including demographic variables and comorbidities. Results: A total of 11 086 patients were included in the analysis. The study group included patients with CKD (5543 patients). Patients in the control group (5543 patients) were propensity matched for age, race, sex, and ethnicity. The primary outcome of in-hospital death or discharge to hospice was observed in 20.96% of patients with CKD compared to 11.91% of the control group with an odds ratio of 1.58 (confidence interval 1.37-1.80). ICU admission was required for 37.20% of patients in the CKD group and 21.63% of patients in the control group (P < .001). Ventilator dependency was found in 14.41% of patients in the CKD group and 8.59% of patients in the control group (P < .01). Development of AKI was seen in 5.65% of patients in the CKD group and 2.90% of patients in the control group (P < .01). A logistic regression model confirmed an independent association between underlying CKD and in-hospital death or discharge to hospice in patients with COVID-19. Conclusion: Our study confirms an independent association between underlying CKD and poor outcomes among hospitalized patients with COVID-19, including in-hospital death or discharge to hospice.

Internal Medicine Residents and the Practice of Defensive Medicine: A Pilot Study Across Three Internal Medicine Residency Programs.

Background Defensive medicine is becoming increasingly prevalent in the United States and is estimated to cost billions of dollars in excess healthcare spending. There is evidence that the practice of defensive medicine starts early in the medical career. Defensive medicine has been investigated among residents in high medico-legal risk specialties, but there is a paucity of information on its prevalence among internal medicine residents. Objective  To examine the prevalence and patterns of defensive medical practices among internal medicine residents. Methods We conducted an online survey among the residents of three internal medicine residency programs in the 2018-2019 academic cycle. We invited all internal medicine residents within the selected programs to participate through email and asked them to complete an electronic survey assessing defensive medical practices. Results A total of 49 out of 143 residents participated in the study (response rate: 34.3%); 55% (n = 27) of the residents who participated considered the risk of being sued during residency to be low, compared to 40.8% (n = 20) who considered it to be moderate and 4.1% (n = 2) who considered it to be high. Defensive medical practices were found to be widely prevalent (40.0-91.3%) among internal medicine residents across all three clinical training stages. Assurance defensive practices were more common than avoidance practices. Conclusion Defensive medical practices, especially of the assurance type, were widely prevalent among our sample of internal medicine residents.

Patterns of medical student engagement in a second-year pathophysiology course: relationship to USMLE Step 1 performance.

Historically, attendance has been a marker of academic performance, but the current medical education literature has had mixed results. In addition, attendance is dropping in the preclinical curricula, whereas, at the same time, the focus on United States Medical Licensing Examination Step 1 performance is increasing. This present study is a mixed-method approach correlating student attendance and access to the formal curriculum in a second-year pathophysiology course to performance on Step 1. Additionally, survey and focus group data evaluated the usage and importance of both the formal curriculum and third-party resources. Out of 112 eligible students, 77 participated in the study. There was no correlation between attendance or access to the learning materials and Step 1 performance. There was a strong correlation between the performance on the final examination and that of Step 1 (r = 0.813; P < 0.001) and a moderate correlation between formative quiz (r = 0.321; P = 0.005) and individual readiness assessment test performance (r = 0.351; P = 0.002) and Step 1 performance. Survey and focus group data show that students place high importance on faculty-developed materials that they can use on their own, but not attendance. The third-party resources are highly used as an adjunct to the formal curriculum and to focus on Step 1 study. Attendance and access to the formal curriculum do not predict Step 1 performance, whereas performance on high- and low-stakes internal assessments do. Further study on how the lack of social interaction gained from attendance affects development of other competencies and the learning climate are warranted.

Increasing Medical Student Interest in Nephrology.

BACKGROUND: Interest in nephrology careers is declining, possibly due to perceptions of the field and/or training aspects. Understanding practices of medical schools successfully instilling nephrology interest could inform efforts to attract leading candidates to the specialty. METHODS: The American Society of Nephrology Workforce Committee's Best Practices Project was one of several initiatives to increase nephrology career interest. Board-certified nephrologists graduating medical school between 2002 and 2009 were identified in the American Medical Association Masterfile and their medical schools ranked by production. Renal educators from the top 10 producing institutions participated in directed focus groups inquiring about key factors in creating nephrology career interest, including aspects of their renal courses, clinical rotations, research activities, and faculty interactions. Thematic content analysis of the transcripts (with inductive reasoning implementing grounded theory) was performed to identify factors contributing to their programs' success. RESULTS: The 10 schools identified were geographically representative, with similar proportions of graduates choosing internal medicine (mean 26%) as the national graduating class (26% in the 2017 residency Match). Eighteen educators from 9 of these 10 institutions participated. Four major themes were identified contributing to these schools' success: (1) nephrology faculty interaction with medical students; (2) clinical exposure to nephrology and clinical relevance of renal pathophysiology materials; (3) use of novel educational modalities; and (4) exposure, in particular early exposure, to the breadth of nephrology practice. CONCLUSION: Early and consistent exposure to a range of clinical nephrology experiences and nephrology faculty contact with medical students are important to help generate interest in the specialty.

Relationship between classroom attendance and examination performance in a second-year medical pathophysiology class.

Studies completed with undergraduate populations have shown that attendance positively correlates with academic performance. A marked decline in classroom attendance within medical school has recently been noticed with the availability of video capture of lectures and other online material. This study compares these in the era of online material. It took place during the second-year Gastrointestinal and Renal Systems module. Attendance was mandatory at team-based learning and case-based learning sessions on new material and voluntary at lectures (29 sessions) and case-based learning on material previously covered (9 sessions). Attendance was recorded prospectively. All lectures were recorded, and all related files were available to students online. Performance was based on a 118 multiple-choice question final examination. Students voluntarily completed the Motivated Strategies for Learning Questionnaire (MSLQ). The study group consisted of 78 students (68% of 114 total) of whom 48 completed the MSLQ. Mean attendance was 24%, with 33% of students attending none of the nonmandatory sessions. The median score on the final exam for participants was 86.0 (range: 28.8). High levels of self-efficacy and the ability to self-regulate effort were predictive of low attendance. Attendance was positively predicted by an orientation toward peer learning and help seeking. There was no correlation between the percentage of classes attended and performance on the final exam. We conclude that different facets of self-regulated learning predict attendance, with highly confident students being the least likely to attend, and that attendance at in-class sessions is no longer a good marker for performance.

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations.

Quantitative and Qualitative Analysis of the Impact of Adoption of a Mobile Application for the Assessment of Professionalism in Medical Trainees.

PURPOSE: Capturing either lapses or excellence in behaviors related to medical professionalism is difficult. The authors report a mixed-methods analysis of a novel mobile platform for assessing medical professionalism in a training environment. METHOD: A mobile Web-based platform to facilitate professionalism assessment in a situated clinical setting (Professional Mobile Monitoring of Behaviors [PROMOBES]) was developed. A professionalism framework consisting of six domains (reliability, adaptability, peer relationships, upholding principles, team relationships, and scholarship) encompassing 25 subelements underpins the reporting structure. This pilot study involved 26 faculty supervising 93 medical trainees at two sites from January 12 to August 8, 2016. Notable professionalism behaviors were linked to the framework domains and elements; narrative details about incidences were captured on mobile devices. Surveys gauged the technological functionality and impact of PROMOBES on faculty assessment of professionalism. Qualitative focus groups were employed to elucidate user experience. RESULTS: Although users anticipated PROMOBES's utility would be for reporting lapses in professionalism, 94.7% of reports were for commendation. Comfort assessing professionalism (P = .04) and recognition of the reporting procedures for professionalism-related concerns (P = .01) improved. PROMOBES attained high acceptance ratings. Focus group analysis revealed that the explicit connection to the professionalism framework was powerful; similarly, the near real-time reporting capability, multiple observer inputs, and positive feedback facilitation were strengths. CONCLUSIONS: Making the professionalism framework visible and accessible via a mobile platform significantly strengthens faculty knowledge and behaviors regarding assessment. The strong desire to capture positive behaviors was an unexpected finding.

Renal cell carcinoma with isolated breast metastasis.

Renal cell carcinoma (RCC) is a highly prevalent disease worldwide with many cases being metastasised to various organs during the time of initial presentation. Metastatic RCC to the breast is a rare entity and can mimic primary breast carcinoma. In this article, we present a 63-year-old Caucasian woman presented with a breast mass that was detected by screening mammography and found to have a biopsy proven grade-II clear RCC in the breast tissue. Despite the high incidence and prevalence of primary breast cancer, metastasis from extramammary should be suspected in patients with a prior history of other cancers. In this brief literature review, we also highlight the survival benefit from surgery and close follow-up in selected group of patients with metastatic, metachronous and solitary RCC.

Team-based learning in large enrollment classes.

The goal of this review is to highlight the key elements needed to successfully deploy team-based learning (TBL) in any class, but especially in large enrolment classes, where smooth logistics are essential. The text is based on a lecture and workshop given at the American Physiological Society's Institute on Teaching and Learning in Madison, WI, in June 2016. After a short overview of the TBL method, its underpinning in learning theory, and a summary of current evidence for its effectiveness, we present two case studies from our own teaching practices in a new medical school. The first case study explores critical elements of design and planning for a TBL module, and the second explores best practices in classroom management. As medical educators in the fields of physiology, pediatrics, nephrology, and family medicine, we present the objective views of subject matter experts who adopted TBL as one teaching method rather than TBL experts or advocates per se. The review is aimed primarily at faculty contemplating using TBL for the first time who are interested in exploring the significant benefits and challenges of TBL.

Application of a utility analysis to evaluate a novel assessment tool for clinically oriented physiology and pharmacology.

Multiple-choice questions are a gold-standard tool in medical school for assessment of knowledge and are the mainstay of licensing examinations. However, multiple-choice questions items can be criticized for lacking the ability to test higher-order learning or integrative thinking across multiple disciplines. Our objective was to develop a novel assessment that would address understanding of pathophysiology and pharmacology, evaluate learning at the levels of application, evaluation and synthesis, and allow students to demonstrate clinical reasoning. The rubric assesses student writeups of clinical case problems. The method is based on the physician's traditional postencounter Subjective, Objective, Assessment and Plan note. Students were required to correctly identify subjective and objective findings in authentic clinical case problems, to ascribe pathophysiological as well as pharmacological mechanisms to these findings, and to justify a list of differential diagnoses. A utility analysis was undertaken to evaluate the new assessment tool by appraising its reliability, validity, feasibility, cost effectiveness, acceptability, and educational impact using a mixed-method approach. The Subjective, Objective, Assessment and Plan assessment tool scored highly in terms of validity and educational impact and had acceptable levels of statistical reliability but was limited in terms of acceptance, feasibility, and cost effectiveness due to high time demands on expert graders and workload concerns from students. We conclude by making suggestions for improving the tool and recommend deployment of the instrument for low-stakes summative assessment or formative assessment.

Uric Acid as a Marker of Kidney Disease: Review of the Current Literature.

Uric acid has been implicated in the pathophysiology of renal disease; however renal clearance makes a causal relationship difficult to prove. We examine the current literature to support a potential role of uric acid in the development of kidney disease and to determine the potential to use uric acid as a marker for future renal decline. After review, we conclude that uric acid is definitively linked to the development of chronic kidney disease and can be a poor prognostic factor for the development of acute renal failure, as well. However, further human research is needed before predictive models utilizing uric acid can be developed and used in the clinical setting.

Update on clinical trials for the prevention of acute kidney injury in patients undergoing cardiac surgery.

BACKGROUND: Effective therapeutic agents for the prevention and treatment of acute kidney injury (AKI) after cardiac surgery remain elusive despite the tremendous advances in surgical techniques, technology, and understanding of disease processes. Recent developments and their effect on the incidence of AKI after cardiac surgery are discussed. DATA SOURCES: Published clinical trials in PubMed, strength of evidence assessed by the guidelines of the American Family Physicians. CONCLUSIONS: The definition of AKI has changed, and the focus of interventions has shifted from treatment to prevention to recovery from AKI. Antioxidants and biological agents have been added to classic armaments of hydration and diuretics in addition to tighter metabolic control to prevent AKI. Although the treatment options remain unsatisfactory, a lot of progress nevertheless continues to be made in the prevention and treatment of AKI.

A physiologic-based approach to the treatment of a patient with hypokalemia.

Hypokalemia is common and can be associated with serious adverse consequences, including paralysis, ileus, cardiac arrhythmias, and death. As a result, the body maintains serum potassium concentration within very narrow limits by tightly regulated feedback and feed-forward systems. Whereas the consequences of symptomatic hypokalemia and severe potassium depletion are well appreciated, chronic mild hypokalemia can accelerate the progression of chronic kidney disease, exacerbate systemic hypertension, and increase mortality. Persistent hypokalemia may reflect total-body potassium depletion or increased renal potassium clearance. In a patient with simple potassium depletion, potassium replacement therapy should correct serum potassium concentration, but may have little effect when renal potassium clearance is abnormally increased from potassium wasting. In such cases, the addition of potassium-sparing diuretics might be helpful. Serum potassium concentration is an inaccurate marker of total-body potassium deficit. Mild hypokalemia may be associated with significant total-body potassium deficits and conversely, total-body potassium stores can be normal in patients with hypokalemia due to redistribution. The speed and extent of potassium replacement should be dictated by the clinical picture and guided by frequent reassessment of serum potassium concentration(.) The goals of therapy should be to correct a potassium deficit, if present, without provoking hyperkalemia. Oral replacement is preferred except when there is no functioning bowel or in the setting of electrocardiogram changes, neurologic symptoms, cardiac ischemia, or digitalis therapy.

Post-operative serum uric acid and acute kidney injury.

BACKGROUND: We hypothesized that post-operative serum uric acid (SUA) may be associated with acute kidney injury (AKI). METHODS: In this prospective, observational study, the relationships between SUA, urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18), serum monocyte chemoattractant protein-1 (sMCP-1) and tumor necrosis factor-alpha (sTNF-alpha), and incidence of AKI were determined. SUA were divided into tertiles and their association with AKI investigated. RESULTS: A total of 100 cardiac surgery patients were included for analyses. The 1st, 2nd, and 3rd SUA tertiles were associated with 15.1%, 11.7%, and 54.5% incidence of AKI, respectively. The 3rd SUA tertile, compared to the referent 1st tertile, was associated with an eightfold (OR 8.38, CI95% 2.13-33.05, p=0.002) increased risk for AKI. Patients with AKI on post-operative day 1 (n=11) were then excluded for the purpose of determining the predictive value of SUA to diagnose AKI on postoperative day 2 and during hospital stay. In comparison to the referent 1st tertile, the 3rd tertile SUA was associated with an eightfold increased risk for AKI on post-operative day 2 (adjusted OR 7.94, CI95% 1.50-42.08, P=.015) and a five-fold increased risk for AKI during hospital stay (OR 4.83, CI95% 1.21-19.20, P=.025), respectively. SUA (Area Under Curve, AUC 0.77 (CI95% 0.66-0.88, P<.001), serum creatinine (0.73, CI95% 0.62-0.84, P<.001) and sTNF-alpha (0.76, CI95% 0.65-0.87, P<.001) had the best diagnostic performance measured by the Receiver Operating Characteristics curves. CONCLUSIONS: We conclude that post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI.

Rituximab in immunologic glomerular diseases.

Experimental data suggest that the B-cell antigen CD20 may play a significant role in the pathogenesis of many diseases including glomerular diseases. These and other findings underpin the central concept of B-cell-depleting therapies that target CD20 antigen as treatments for lupus nephritis, idiopathic membranous nephropathy, focal segmental glomerulosclerosis, cryglobulinemic glomerulonephritis, antibody mediated renal allograft rejection and recurrent glomerulonephritis in renal allograft. Use of rituximab as a B-cell depleting therapy has been associated with clinical improvement and has emerged as a possible adjunct or alternative treatment option in this field of nephrology.

Perioperative fluid balance and acute kidney injury.

BACKGROUND: Positive fluid balance (FB) has been linked to adverse clinical outcomes. We performed this study to explore the relationship between perioperative fluid balance and acute kidney injury (AKI). METHODS: The relationships between FB and AKI were explored using a prospective, observational design. Patients were divided into quartiles based on FB status in the first 24 h from initiation of surgery in order to further explore this relationship. RESULTS: One hundred adult patients undergoing cardiovascular surgery were included in the analysis. The major finding of the study was that positive FB occurred early in the intraoperative period and progressed into the postoperative period and that fluid administration was not clearly associated with any identifiable volume-sensitive event. The evolution of positive FB preceded the rise in serum creatinine. Progressive severity of positive FB was associated with increased incidence of AKI. The highest quartile FB group had a five-fold increased risk for AKI (adjusted odds ratio 4.98, 95 % confidence interval 1.38-24.10, p = 0.046) compared to the lowest quartile group, higher postoperative peak serum creatinine values (p < 0.001), surgery-related complications (p < 0.001) and intensive care unit (p < 0.001) and hospital length of stay (p = 0.048). CONCLUSIONS: Positive FB was associated with increased incidence of AKI.

Hand-carried echocardiography by hospitalists: a randomized trial.

BACKGROUND: Hospitalists can use hand-carried echocardiography for accurate point-of-care information, but patient outcome data for its application are sparse. METHODS: We performed an unblinded, parallel-group randomized trial between July 2008 and March 2009 at one teaching hospital in Chicago, Illinois. We randomly assigned adult general medicine inpatients referred for standard echocardiography with indications investigatable by hand-carried echocardiography to care guided by hand-carried echocardiography or usual care. The main outcome measure was length of stay on the referring hospitalist's service. Secondary outcomes included a before-after analysis of reported changes in management due to hand-carried echocardiography and the diagnostic accuracy of hand-carried echocardiography. RESULTS: The difference in length of stay between 226 participants randomized to care guided by hand-carried echocardiography (geometric mean 46.1 hours, interquartile range 29.0-70.9 hours) and 227 participants randomized to usual care (46.9 hours, interquartile range 34.1-68.3 hours) corresponded to a 1.7% reduction in length of stay that was not statistically significant (95% confidence interval, -12.1 to 9.8%). In post hoc subgroup analyses, care guided by hand-carried echocardiography reduced length of stay in participants who were referred for heart failure (P=.0008). Among participants who underwent both hand-carried and standard echocardiography, hospitalists changed management due to hand-carried echocardiography in 37%. Despite the favorable diagnostic accuracy of hand-carried echocardiography, most changes to the timing of hospital discharge occurred after standard echocardiography. CONCLUSION: Hospitalist care guided by hand-carried echocardiography for unselected general medicine patients does not meaningfully affect length of stay. Whether or not it affects care quality remains unstudied.

Anaerobic clavicular osteomyelitis following colonoscopy in a hemodialysis patient.

Patients on dialysis are immunocompromised and are therefore susceptible to both common and unusual infectious complications. These infections are often related to their dialysis access but even routine diagnostic tests unrelated to dialysis can also lead to rare adverse events. We present an unusual case of clavicular osteomyelitis from Bacteroides fragilis in a patient on maintenance hemodialysis following colonoscopy. The risk factors for this unusual site of infection, the incidence and guidelines for prophylactic antibiotic administration are discussed here.