Smart-phone Based Geofencing: A Novel Approach to Monitoring Clinical Work Hours in Surgery Residency.

OBJECTIVE: The Accreditation Council for Graduate Medical Education specifies strict requirements for clinical work hours during residency training, with serious consequences for violations. Self-reporting of work hours by trainees can be inaccurate due to recall bias, giving program directors limited data to influence change. We aimed to assess the impact of a smart-phone based geofencing application on submission rates for work hours and reported violations in a general surgery residency program at a university-based medical center. We also examined resident perceptions surrounding implementation and use of the application. METHODS: We compared clinical work hours submitted and violations reported during the pilot period (October-November 2019) with the months prior to the launch of the application (July-August 2019). PGY1 and PGY2 residents were eligible to use the application during and after this pilot period. Semi-structured interviews were used to assess resident perceptions. A retrospective review was conducted to compare reporting during the same time period from the prior academic year (2018-2019) for historical reference. Paired t-tests were used to analyze the data. RESULTS: Twenty-six residents (15 PGY1, 11 PGY2) were eligible for the intervention and 23 residents (88%) used the application. The mean number of violations reported decreased significantly during the pilot period compared with the months prior to the intervention (4.5 vs. 11, p = 0.04). The total rate of submissions was not significantly different after the intervention (85% vs. 82%, p = 0.42). The PGY1 mean submission rate decreased during the pilot period (91%-75%, p = 0.21) while the PGY2 submission rate increased (77%-91%, p = 0.07). Compared with historical data, there was an increase in overall total submission rates between academic years 2018/2019 and 2019/2020 (74% vs. 79%, p = 0.047) and an associated decrease in the mean number of monthly violations (14 vs. 6.25, p = 0.004). Thirteen (50%) residents (8 PGY1, 5 PGY2) volunteered for semi-structured interviews. Most participants found the application useful for recording and reporting clinical work hours. They noted an ease in the administrative burden as well as more accurate reporting associated with automated logging. Use of the application was not perceived to limit engagement with patient care; however, there were privacy concerns and some technical barriers were identified. The messaging regarding the application's use was identified as critical for implementation. CONCLUSIONS: The "real-time" data provided by a geofencing application in our program helped to reduce the number of work-hour violations reported and did not diminish resident engagement with patient care. Decreasing the administrative burden of recording work hours coupled with improving transparency and accuracy of submissions may be important mechanisms.

A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD.

BACKGROUND: Exposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure-while reducing the need for red blood cell transfusions-is unknown. METHODS: In this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 µg/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician. RESULTS: There were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µg) compared with the titration-dose group (53.6 µg median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) µg and 53.6 (31.1, 89.9) µg, respectively; the median of the difference between treatment groups was -22.1 (95% CI, -26.1 to -18.1) µg. CONCLUSIONS: These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing.

Nephrology in the Academic Intensive Care Unit: A Qualitative Study of Interdisciplinary Collaboration.

RATIONALE & OBJECTIVE: Collaboration between nephrology consultants and intensive care unit (ICU) teams is important in light of the high incidence of acute kidney injury in today's ICUs. Although there is considerable debate about how nephrology consultants and ICU teams should collaborate, communicative dynamics between the 2 parties remain poorly understood. This article describes interactions between nephrology consultants and ICU teams in the academic medical setting. STUDY DESIGN: Focused ethnography using semi-structured interviews and participant observation. SETTING & PARTICIPANTS: Purposive sampling was used to enroll nephrologists, nephrology fellows, and ICU practitioners across several roles collaborating in 3 ICUs (a medical ICU, a surgical ICU, and a cardiothoracic surgical ICU) of a large urban US academic medical center. Participant observation (150 hours) and semi-structured interviews (35) continued until theoretical saturation. ANALYTICAL APPROACH: Interview and fieldnote transcripts were coded in an iterative team-based process. Explanation was developed using an abductive approach. RESULTS: Nephrology consultants and surgical ICU teams exhibited discordant preferences about the aggressiveness of renal replacement therapy based on different understandings of physiology, goals of care, and acuity. Collaborative difficulties resulting from this discordance led to nephrology consultants often serving as dialysis proceduralists rather than diagnosticians in surgical ICUs and to consultants sometimes choosing not to express disagreements about clinical care because of the belief that doing so would not lead to changes in the course of care. LIMITATIONS: Aspects of this single-site study of an academic medical center may not be generalizable to other clinical settings and samples. Surgical team perspectives would provide further detail about nephrology consultation in surgical ICUs. The effects of findings on patient care were not examined. CONCLUSIONS: Differences in approach between internal medicine-trained nephrologists and anesthesia- and surgery-trained intensivists and surgeons led to collaborative difficulties in surgical ICUs. These findings stress the need for medical teamwork research and intervention to address issues stemming from disciplinary siloing rooted in long-term socialization to different disciplinary practices.

Iron Regulation by Molidustat, a Daily Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: The current treatment for anemia associated with chronic kidney disease (CKD) includes the administration of erythropoiesis stimulating agents (ESAs) combined with iron supplementation. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has potential to treat anemia associated with CKD through increased erythropoietin production and improved iron availability. Here, we report the effect of molidustat on iron metabolism. METHOD: Parameters of iron metabolism were monitored in three 16-week, randomized, controlled, phase 2 studies assessing the safety and efficacy of molidustat in the treatment of anemia associated with CKD in different populations: treatment-naïve and previously ESA-treated patients not on dialysis, and previously ESA-treated patients on hemodialysis. Iron supplementation was left at the discretion of the investigator. RESULTS: In treatment-naïve patients not on dialysis, transferrin saturation (TSAT), hepcidin, ferritin, and iron concentrations decreased with molidustat, whereas total iron binding capacity (TIBC) increased. Similar results were observed in previously ESA-treated patients not on dialysis, although changes in those parameters were larger in treatment-naïve than in previously ESA-treated patients. In previously ESA-treated patients receiving hemodialysis, hepcidin concentration and TIBC remained stable with molidustat, whereas TSAT and ferritin and iron concentrations increased. Generally, similar trends were observed in secondary analyses of subgroups of patients not receiving iron supplementation. CONCLUSIONS: Molidustat is a potential alternative to standard treatment of anemia associated with CKD, with a different mechanism of action. In patients not receiving dialysis, molidustat increases iron availability. In patients receiving hemodialysis, further investigation is required to understand fully the mechanisms underlying iron mobilization associated with molidustat.

Long-Term Efficacy and Safety of Molidustat for Anemia in Chronic Kidney Disease: DIALOGUE Extension Studies.

BACKGROUND: Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat. METHODS: Both studies were parallel-group, open-label, multicenter studies of ≤36 months' duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs). RESULTS: In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient's overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group. CONCLUSIONS: Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.

Effects of Molidustat in the Treatment of Anemia in CKD.

BACKGROUND AND OBJECTIVES: The efficacy and safety of molidustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, have been evaluated in three 16-week, phase 2b studies in patients with CKD and anemia who are not on dialysis (DaIly orAL treatment increasing endOGenoUs Erythropoietin [DIALOGUE] 1 and 2) and in those who are on dialysis (DIALOGUE 4). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: DIALOGUE 1 was a placebo-controlled, fixed-dose trial (25, 50, and 75 mg once daily; 25 and 50 mg twice daily). DIALOGUE 2 and 4 were open-label, variable-dose trials, in which treatment was switched from darbepoetin (DIAGLOGUE 2) or epoetin (DIALOGUE 4) to molidustat or continued with the original agents. Starting molidustat ranged between 25-75 and 25-150 mg daily in DIAGLOGUE 2 and 4, respectively, and could be titrated to maintain hemoglobin levels within predefined target ranges. The primary end point was the change in hemoglobin level between baseline and the mean value from the last 4 weeks of the treatment period. RESULTS: In DIAGLOGUE 1 (n=121), molidustat treatment was associated with estimated increases in mean hemoglobin levels of 1.4-2.0 g/dl. In DIAGLOGUE 2 (n=124), hemoglobin levels were maintained within the target range after switching to molidustat, with an estimated difference in mean change in hemoglobin levels between molidustat and darbepoetin treatments of up to 0.6 g/dl. In DIAGLOGUE 4 (n=199), hemoglobin levels were maintained within the target range after switching to molidustat 75 and 150 mg, with estimated differences in mean change between molidustat and epoetin treatment of -0.1 and 0.4 g/dl. Molidustat was generally well tolerated, and most adverse events were mild or moderate in severity. CONCLUSIONS: The overall phase 2 efficacy and safety profile of molidustat in patients with CKD and anemia enables the progression of its development into phase 3.

Accuracy of Acid-Base Diagnoses Using the Central Venous Blood Gas in the Medical Intensive Care Unit.

BACKGROUND: Acid-base disturbances are frequent in critically ill patients. Arterial blood gas (ABG) is the gold standard in the diagnosis of these disturbances, but it is invasive with potential hazards. For patients with a central venous catheter, venous blood gas (VBG) sampling may be an alternative, less-invasive diagnostic tool. However, the accuracy of a central VBG-based acid-base disorder diagnosis compared to an ABG is unknown. The primary objective of this study was to assess the accuracy of a central VBG-based acid-base disorder diagnosis compared to the "gold standard" ABG in critically ill patients. METHODS: This was a study of adult patients in a medical intensive care unit that had simultaneously drawn ABG and central VBG samples. Expert acid-base diagnosticians, all nephrologists, diagnosed the acid-base disorder(s) in each blood gas sample. The central VBG diagnostic accuracy was assessed with percent agreement, sensitivity, and specificity compared to the ABG-based diagnosis. RESULTS: The study involved 23 participants. Overall, the central VBG had 100% sensitivity for metabolic acidosis, metabolic alkalosis, and respiratory acidosis, and lower sensitivity (71%) for respiratory alkalosis, and high percent agreement, ranging from 75 to 94%. VBG-based diagnoses in vasopressor-dependent patients (n = 13, 56.5%) performed similarly to the entire sample. CONCLUSIONS: In critically ill adult patients, central VBG may be used to detect and diagnose acid-base disturbances with reasonable diagnostic accuracy, even in shock states, compared to the ABG. This study supports the use of central VBG for diagnosis of acid-base disturbances in critically ill patients.

Risk of complications with use of aspirin during renal biopsy: A systematic review.

BACKGROUND: Bleeding is a well-known complication of percutaneous renal biopsy (PRB). Thus, antiplatelet agents are routinely held for most patients undergoing elective PRB to decrease bleeding risk. MATERIALS AND METHODS: In this systematic review, we examine the association between antiplatelet use and bleeding during PRB. MEDLINE and EMBASE were searched from inception to December 2016 using terms that included "renal biopsy", "antiplatelet","aspirin", and "bleeding". Guidelines and systematic reviews were identified primarily through large databases, including the National Guideline Clearinghouse and Cochrane Database of Systematic Reviews. Two authors independently screened the results, and appraised and graded the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Out of 371 guidelines, 40 systematic reviews, and 709 primary studies originally identified, 4 guidelines, 1 systematic review, and 2 primary studies met inclusion criteria. The guidelines recommend halting aspirin for elective PRB. The systematic review found no difference in major outcomes for PRB in patients for whom aspirin was continued versus halted, but was of low quality. The 2 nonrandomized primary studies in PRB patients managed with and without aspirin found no difference in major bleeds but a higher risk of minor bleeds. CONCLUSIONS: There is low-quality evidence on the effect of aspirin on bleeding risk from PRB. It is reasonable to discontinue aspirin 7 - 10 days prior to nonemergent biopsies, in accordance with guidelines. Given the results from the primary studies, it is reasonable to perform randomized controlled trials to obtain high-quality evidence to inform clinical practice.
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Interpretation of the Kidney Disease: Improving Global Outcomes guidelines for iron therapy: commentary and emerging evidence.

The 'Kidney Disease: Improving Global Outcomes' (KDIGO) Clinical Practice Guideline for Anaemia in Chronic Kidney Disease includes detailed recommendations for the use of iron therapy in a variety of clinical circumstances. However, the evidence base regarding the use of iron therapy in patients with chronic kidney disease was relatively incomplete at the time the guideline was developed. As a result, there has been significant debate as to the appropriate use of iron therapy in this population. In this article, the KDIGO guidelines are discussed in the context of recently published commentary pieces and additional research to provide a richer context in which to interpret and understand the guidelines.

Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores.

The Native Kidney Biopsy: Update and Evidence for Best Practice.

The kidney biopsy is the gold standard in the diagnosis and management of many diseases. Since its introduction in the 1950s, advancements have been made in biopsy technique to improve diagnostic yield while minimizing complications. Here, we review kidney biopsy indications, techniques, and complications in the modern era. We also discuss patient populations in whom special consideration must be given when considering a kidney biopsy and the important role that the kidney biopsy plays in nephrology training. These data are presented to develop best practice strategies for this essential procedure.

Kidney diseases associated with haematological cancers.

Advances in chemotherapy for haematological malignancies, resulting from a greater understanding of the complex pathophysiology of these diseases, have improved the survival of patients with these disorders. Clinicians must now, therefore, be more aware of the issues related to fluid, electrolyte, and acid-base disorders, as well as acute and chronic kidney injuries that can develop in such patients as a result of the underlying malignancy and its treatment. Patients with acute kidney injury associated with haematological malignancy have a worse prognosis than do other patients with acute kidney injury. Glomerular diseases associated with haematological malignancies are thought to be paraneoplastic syndromes with variable histological presentations. Some of the newest therapeutic agents used to treat haematological malignancies have adverse renal effects that can preclude continuation of treatment, often leading to difficult clinical decisions when patients have advanced disease and alternative treatment options are limited. Haematopoietic stem cell transplantation has an expanding role as a therapy for haematological malignancies but is also associated with important renal complications. Here, we review the literature that examines the incidences, aetiologies, mechanisms and treatment options for renal disorders associated with haematological malignancies.

Clinical Decision Making in a Patient with Stage 5 CKD--Is eGFR Good Enough?

The development and widespread use of serum creatinine concentration-based prediction equations to calculate eGFR have been major advances for detection of patients with CKD and the epidemiologic study of CKD and its outcomes. However, these equations as well as those that also incorporate serum cystatin C concentration provide GFR estimates that, although reasonably precise on average, can differ markedly and in clinically important ways from actual GFR. Thus, it is important that clinicians who use these equations for clinical decision-making be familiar with their strengths and weaknesses and have an appreciation of their potential for error. More precise knowledge of actual GFR is important in certain clinical circumstances, including, as presented in this Attending Rounds, patients with stage 5 CKD, in whom decisions regarding dialysis initiation are necessary. Nephrologists should have the ability to accurately determine GFR when needed if clinical circumstances suggest inaccuracy of the calculated eGFR reported by the clinical laboratory.

Erythropoietin and resistant hypertension in CKD.

There is a well-documented association between erythropoiesis-stimulating agents (ESAs) and hypertension in chronic kidney disease. Studies suggest that the mechanism for this is multifactorial. First, some chronic kidney disease patients may have a limited ability to accommodate a rapid increase in red cell volume because of a decreased glomerular filtration rate, left ventricular hypertrophy, and decreased arterial compliance. Second, there is likely a direct vasoconstrictor effect of ESAs. Although no large randomized controlled trials of ESAs have been designed with blood pressure as an a priori outcome, several meta-analyses have explored this relationship and generally support the existence of ESA-induced hypertension. There are as of yet no data directly linking ESA-induced hypertension with increased cardiovascular morbidity and mortality. Despite this, clinicians should be vigilant for ESA-induced hypertension, use caution when using ESAs in patients with resistant hypertension, and be attentive to the rate of hemoglobin increase in patients with poorly controlled blood pressure.

Routine screening for CKD should be done in asymptomatic adults... selectively.

CKD is an important public health problem associated with substantial morbidity, impaired quality of life, shortened life expectancy, and excessive health care costs. Given its long preclinical latency, screening of asymptomatic individuals for CKD has been considered as a potentially useful means of early detection, with a goal of reducing CKD progression and its complications. A recent clinical practice guideline from the American College of Physicians that recommended against screening for CKD in asymptomatic adults without risk factors has reignited debate regarding CKD screening. Despite the lack of randomized controlled trial evidence showing benefits of CKD screening, even among individuals at increased risk for CKD, such as those with diabetes or hypertension or who are of certain high-risk racial or ethnic groups, a thoughtful and selective approach to CKD screening seems to be cost-effective and clinically valuable. CKD screening is recommended by several nephrology professional societies and appropriate in at-risk asymptomatic individuals with the intent of identifying and managing CKD, diagnosing the etiology of CKD, limiting or preventing CKD progression and its associated cardiovascular disease risk, and minimizing risk of AKI, inappropriate drug dosing, and nephrotoxic injury.