Management of urothelial cancer in patients with chronic kidney disease receiving platinum-based chemotherapy.

Despite recent advances in the management of urothelial cancer (UC), cisplatin-based combination chemotherapy regimens remain critical. However, their use can be complicated in patients with chronic kidney disease (CKD), which is not uncommon in UC patients. Based on the Galsky criteria for cisplatin ineligibility, most patients with CKD will be excluded from receiving cisplatin-based chemotherapy altogether. For patients with borderline kidney function, several strategies - such as the use of split-dose cisplatin, dose reductions, or extra hydration - may facilitate the use of cisplatin, but these need to be prospectively validated. This review highlights the critical need for a multidisciplinary team, including onco-nephrologists, to help manage renal complications and optimize delivery of cancer care in complex UC patients with CKD.

In patients with urothelial cancer, the presence of chronic kidney disease can significantly impact treatment options, eligibility for clinical trials, and overall patient outcomes. This review discusses key strategies and newer treatment options that can be used to optimize outcomes in patients who often can't receive standard treatments. Importantly, this article also highlights the critical importance and need for a multidisciplinary team of specialists, including kidney specialists with a focus on cancer patients, to help manage kidney function and deliver high-quality care to patients with urothelial cancer and chronic kidney disease.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

PURPOSE: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. METHODS: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses. RESULTS: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications. CONCLUSION: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients.

Moral Controversy and Working with Colleagues with a Shared Ethical/Moral Outlook: A National Survey of US Primary Care Physicians.

OBJECTIVES: This study assesses physicians' attitudes on the importance of working with colleagues who share the same ethical or moral outlook regarding morally controversial healthcare practices and examines the association of physicians' religious and spiritual characteristics with these attitudes. METHODS: We conducted a secondary data analysis of a 2009 national survey that was administered to a stratified random sample of 1504 US primary care physicians (PCPs). In that dataset, physicians were asked: "For you personally, how important is it to work with colleagues who share your ethical/moral outlook regarding morally controversial health care practices?" We examined associations between physicians' religious/spiritual characteristics and their attitudes toward having a shared ethical/moral outlook with colleagues. RESULTS: Among eligible respondents, the response rate was 63% (896/1427). Overall, 69% of PCPs indicated that working with colleagues who share their ethical/moral outlook regarding morally controversial healthcare practices was either very important (23%) or somewhat important (46%). Physicians who were more religious were more likely than nonreligious physicians to report that a shared ethical/moral outlook was somewhat/very important to them (P < 0.001 for all measures of religiosity, including religious affiliation, attendance at religious services, intrinsic religiosity, and importance of religion as well as spirituality). Physicians with a high sense of calling were more likely than those with a low sense of calling to report a high importance of having a shared ethical/moral outlook with colleagues regarding morally controversial healthcare practices (multivariate odds ratio 2.5, 95% confidence interval 1.5-4.1). CONCLUSIONS: In this national study of PCPs, physicians who identified as religious, spiritual, or having a high sense of calling were found to place a stronger emphasis on the importance of shared ethical/moral outlook with work colleagues regarding morally controversial healthcare practices. Moral controversy in health care may pose a particular challenge for physicians with lower commitments to theological pluralism.

Techniques and Trends, Success Rates, and Adverse Events in Emergency Department Pediatric Intubations: A Report From the National Emergency Airway Registry.

STUDY OBJECTIVE: We describe emergency department (ED) intubation practices for children younger than 16 years through multicenter prospective surveillance. METHODS: Academic and community EDs in the United States, Canada, and Australia recorded data electronically, from 2002 to 2012, with verified greater than or equal to 90% reporting. RESULTS: Ten of 18 participating centers provided qualifying data, reporting 1,053 encounters. Emergency physicians initiated 85% of intubations. Trainees initiated 83% (95% confidence interval [CI] 81% to 85%). Premedication became uncommon, reaching less than 30% by the last year. Etomidate was used in 78% of rapid sequence intubations. Rocuronium use increased during the period of study, whereas succinylcholine use declined. Video laryngoscopy increased, whereas direct laryngoscopy declined. The first attempt was successful in 83% of patients (95% CI 81% to 85%) overall. The risk of first-attempt failure was highest for infants (relative risk versus all others 2.3; 95% CI 1.8 to 3.0). Odds of first-attempt success for girls relative to boys were 0.57. The odds were 3.4 times greater for rapid sequence intubation than sedation without paralysis. The ultimate success rate was 99.5%. CONCLUSION: Because we sampled only 10 centers and most of the intubations were by trainees, our results may not be generalizable to the typical ED setting. We found that premedication is now uncommon, etomidate is the predominant induction agent, and rocuronium and video laryngoscopy are used increasingly. First-attempt failure is most common in infants.

Failure of antibiotics in cellulitis trials: a systematic review and meta-analysis.

OBJECTIVES: The objectives of the study are to quantify trial-to-trial variability in antibiotic failure rates, in randomized clinical trials of cellulitis treatment and to provide a point estimate for the treatment failure rate across trials. METHODS: We conducted a structured search for clinical trials evaluating antibiotic treatment of cellulitis, indexed in PubMed by August 2015. We included studies published in English and excluded studies conducted wholly outside of developed countries because the pathophysiology of cellulitis is likely to be different in such settings. Two authors reviewed all abstracts identified for possible inclusion. Of studies identified initially, 5% met the selection criteria. Two reviewers extracted data independently, and data were pooled using the Freeman-Tukey transformation under a random-effects model. Our primary outcome was the summary estimate of treatment failure across intent-to-treat and clinically evaluable participants. RESULTS: We included 19 articles reporting data from 20 studies, for a total of 3935 patients. Treatment failure was reported in 6% to 37% of participants in the 9 trials reporting intent-to-treat results, with a summary point estimate of 18% failing treatment (95% confidence interval, 15%-21%). In the 15 articles evaluating clinically evaluable participants, treatment failure rates ranged from 3% to 42%, and overall, 12% (95% confidence interval, 10%-14%) were designated treatment failures. CONCLUSIONS: Treatment failure rates vary widely across cellulitis trials, from 6% to 37%. This may be due to confusion of cellulitis with its mimics and perhaps problems with construct validity of the diagnosis of cellulitis. Such factors bias trials toward equivalence and, in routine clinical care, impair quality and antibiotic stewardship. Objective diagnostic tools are needed.

Split-Dose Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Carcinoma: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: Gemcitabine plus cisplatin (GC) is a highly active and commonly used regimen in locally advanced/metastatic urothelial carcinoma (la/mUC). With GC, cisplatin is dosed at 70 mg/m2 on day 1 of a 3-week cycle; however, for many patients, impaired renal or cardiac function, neuropathy, or poor performance status (PS) can preclude the use of cisplatin. A promising alternative is split-dose GC, in which the cisplatin dose is divided over 2 days. METHODS: We conducted a systematic literature review (SLR) and network meta-analysis (NMA) to better understand treatment patterns and comparative effectiveness and safety of split-dose GC vs gemcitabine plus carboplatin (GCa), GC, and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). RESULTS: Among 120 identified studies, 16 studies representing 1,767 patients included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function, age > 70 years, comorbidities, and physician preference. Split-dose GC had objective response rates (ORRs) of 39%-80%, median progression-free survival (PFS) of 3.5-9.9 months, and median overall survival (OS) of 8.5-18.1 months. Discontinuation rates due to adverse events were 5%-38%. In the NMA, ORR with split-dose GC was significantly higher than with GCa. PFS and OS for split-dose GC were similar to that observed with the other regimens (GCa, GC, and MVAC). CONCLUSIONS: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, split-dose GC demonstrated comparable effectiveness and safety profile to those seen with other regimens. Split-dose GC thus has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further prospective study.

Improvement of CRB-65 as a prognostic scoring system in adult patients with bacteraemic pneumococcal pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of hospitalization among infectious diseases, and is mainly caused by Streptococcus pneumoniae. Modifications were tested to improve the accuracy of CRB-65 as a simple but useful bedside scoring system, and to compare it with 3 established severity scoring systems (PSI, CURB-65 and CRB-65) to predict 30-day mortality in bacteraemic pneumococcal CAP. METHODS: A retrospective analysis was performed on data from 375 adult patients with bacteraemic pneumococcal pneumonia. Mortality, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic (ROC) curve were calculated for stratifications of the PSI, CURB-65 and CRB-65. The prognostic accuracy after addition of underlying disease and/or a peripheral oxygen saturation (SaO2) < 90% was evaluated (DS CRB-65). RESULTS: The mean age of the patients was 61.5 y, and the 30-day mortality was 9%. Coexisting conditions defined according to the pneumonia severity index (PSI) rule (malignancy, liver, cerebrovascular, and renal disease and congestive heart failure, p = 0.006) and SaO2 < 90% (p < 0.0001) were independently associated with mortality. By adding these variables, the area under the ROC curve of CRB-65 increased from 0.77 (95% confidence interval (CI) 0.66-0.84) to 0.83 (95% CI 0.73-0.89) (p = 0.01), similar to that of PSI (0.84) and CURB-65 (0.81). CONCLUSIONS: Modification of CRB-65 with the addition of 1 point for the presence of any underlying disease according to the PSI rule, and with 1 point if SaO2 was < 90%, increased its prognostic accuracy in bacteraemic pneumococcal pneumonia with retained independence of laboratory data. The modified CRB-65 may have potential use in the assessment of prognosis in patients with CAP.

Significance of the physician's and the patient's sex in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Numerous studies have revealed that the sex of the patient or of the attending physician have impact on patient care, treatment, morbidity and mortality. Community-acquired pneumonia (CAP) is a common cause of hospitalization, antibiotic treatment and intensive care unit (ICU) admission. The purpose of this study was to examine if the patient's or the attending physicians' sex may influence the management of hospitalized patients with CAP. METHODS: Our study included 826 consecutive inpatients with CAP (404 females, and 422 male patients, 429 patients initially treated by a female physician and 397 patients initially treated by a male physician). We examined if the patient's, or the initial attending physician's sex, affected treatment and outcome in patients with CAP. RESULTS: Patients mean age was 69 years, 30-day mortality 9%. By use of the pneumonia severity index, male patients were found to be more severely ill at admission (p = .0008). Fewer female physicians' patients were admitted from the emergency department (ED) to the ICU when compared to male physicians' patients, 5% versus 10% (p = .006), and female physicians' patients received their first intravenous (IV) antibiotic dose later than male physicians' patients in the ED (p = .003). CONCLUSION: Our study indicates that the sex of the attending physician may affect the chosen level of care and antibiotic treatment, and that admitted male patients with CAP were more seriously ill than admitted female patients with CAP.

The Impact of Anonymity in Emergency Medicine Morbidity and Mortality Conferences: Findings from a National Survey of Resident Physicians.

INTRODUCTION: Although the Accreditation Council for Graduate Medical Education mandates structured case review and discussion as a part of residency training, there remains little guidance on how best to structure these conferences to cultivate a culture of safety, promote learning, and ensure that system-based improvements can be made. We hypothesized that anonymous case discussion was associated with a more effective, and less punitive, morbidity and mortality (M&M) conference. Secondarily, we were interested in determining whether this core structural element was correlated with the culture of safety at an institution. METHODS: We conducted a national survey at 33 emergency medicine residency programs evaluating residents' perceptions of M&M and the culture of safety at their institutions. Data was analyzed using descriptive statistics and bivariate analyses. We summarized Likert scores using mean and 95% confidence intervals. We also performed content analysis of the free-text comments and report on the themes identified. RESULTS: There were 1248 residents at the 33 programs surveyed. Of the 1002 who replied (80.3% response rate), 231 respondents reported anonymous case presentations and 744 reported non-anonymous case presentations. Residents at programs with anonymous case presentations were more likely to report that M&M was non-punitive. There were no other significant differences between anonymous and non-anonymous case presentations on any of the culture of safety domains measured. When these comments were systematically analyzed and coded, we found that the comments related to anonymity were both positive and negative. Among the themes identified were anonymity's impact on punitive response to error, the ability to learn from cases, and professional responsibility. CONCLUSION: Anonymous M&Ms are associated with a perception of a less-punitive M&M and with better ratings in several conference-specific outcomes; however, there appears to be no association between the other Agency for Healthcare Research and Quality culture of safety scores and anonymity in M&M.

Real-World Experience of Palbociclib-Induced Adverse Events and Compliance With Complete Blood Count Monitoring in Women With Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer.

BACKGROUND: The cyclin-dependent kinase 4/6 inhibitor palbociclib has emerged as a novel therapeutic agent in metastatic breast cancer. Neutropenia is commonly observed, and thus stringent treatment guidelines regarding complete blood count (CBC) monitoring have been developed. The aim of this study was to provide a real-world experience of the toxicities associated with palbociclib therapy and to evaluate compliance with CBC monitoring. PATIENTS AND METHODS: We performed a retrospective single-center audit of hormone receptor-positive metastatic breast cancer patients treated with palbociclib over a 6-month period in an Irish tertiary referral hospital. RESULTS: A total of 64 patients were included in the analysis. Palbociclib was most commonly used in combination with letrozole (n = 40). A total of 28 patients (44%; 95% confidence interval, 31.2-56.2) had treatment deferrals due to neutropenia, with a median time to first deferral of 4 weeks. Fifteen patients (23%; 95% confidence interval, 15.4-37.7) required dose adjustments; however, there was no association with an increased risk of progressive disease (P = .56). Only 3 patients discontinued treatment as a result of poor tolerance. Adverse events were as expected; however, 7 venous thromboembolic events were reported. CONCLUSION: Compliance was good with existing CBC monitoring guidelines. We observed an 11% incidence of venous thromboembolic events, a significant increase from 2% reported in the PALOMA-3 trial. Further studies are recommended to determine if prophylactic anticoagulation may benefit these patients.

Emergency Medicine Morbidity and Mortality Conference and Culture of Safety: The Resident Perspective.

OBJECTIVE: Morbidity and mortality conference (M&M) is common in emergency medicine (EM) and an Accreditation Council for Graduate Medical Education (ACGME) requirement. We aimed to characterize the prevalence of elements of EM M&M conferences that foster a strong culture of safety. METHODS: Emergency medicine residents at 33 programs across the United States were surveyed using questions adapted from a previously tested survey of EM program directors and the Agency for Healthcare Research and Quality (AHRQ) Culture of Safety Survey. RESULTS: The survey response rate was 80.3% (1,002/1,248). A total of 60.3% (601/997) of residents had not submitted a case of theirs to M&M in the past year. A total of 7.6% (73/954) reported that issues raised at M&M always led to change while 88.3% (842/954) reported that they sometimes did and 4.1% (39/954) reported that they never did. A total of 56.2% (536/954) responded that changes made due to M&M were reported back to the residents. Of residents who had cases presented at M&M, 24.2% (130/538) responded that there was regular debriefing, 65.2% (351/538) responded that there was not, and 10.6% (57/578) were unsure. A total of 10.2% (101/988) of respondents agreed that M&M was punitive, 17.4% were neutral (172/988), and 72.4% (715/988) disagreed. A total of 18.0% (178/987) of residents agreed that they felt pressure to order unnecessary tests because of M&M, 22.3% (220/987) were neutral, and 59.6% (589/987) disagreed. A total of 87.4% (862/986) felt that M&M was a valuable educational didactic session, and 78.3% (766/978) believed that M&M contributes to a culture of safety in their institution. CONCLUSIONS: While most residents believe that M&M is a valuable didactic session and contributes to institutional culture of safety, there are opportunities to improve by communicating changes made in response to M&M, debriefing residents who have had cases presented, and taking steps to make M&M not feel punitive to some residents.

Toward an Objective Diagnostic Test for Bacterial Cellulitis.

BACKGROUND: Prior studies repeatedly showed that cultures of skin lesions diagnosed as "cellulitis" are usually negative. However, lack of a gold standard for diagnosis (against which culture might be judged) and failure to assess the human immune response are important limitations of prior work. In this pilot study, we aimed to develop a criterion standard for research on bacterial cellulitis, to evaluate the sensitivity of procalcitonin for bacterial cellulitis, and to use gene expression analysis to find other candidate diagnostic markers. METHODS: We classified lesions via biopsies, 16s rRNA gene detection, culture, and histopathology. We quantified procalcitonin expression in blood. We also used Nanostring technology to quantify transcription of immunomodulators that may distinguish cases from inflamed controls. RESULTS: Of 28 participants, 15 had a clinical diagnosis of cellulitis, six had a diagnosis of non-infectious dermatitis, and seven were normal volunteers. Of the "cellulitis" patients, three (20%) had pathogens isolated, and were designated confirmed cases. Procalcitonin was undetectable in all three. HLA-DQA1 was expressed 34-fold more in confirmed cases vs. controls (fold change of geometric mean). Heat maps depicting multiplex gene expression analysis revealed a distinct profile of gene expression in confirmed cases relative to comparators. CONCLUSIONS: Most "cellulitis" patients had microbiologically-negative biopsies. Procalcitonin was undetectable, and HLA-DQA1 elevated, in confirmed bacterial cases. Multivariable transcriptomic profiling results supported our algorithm's ability to identify patients with true bacterial cellulitis. A larger sample may allow discovery of an immunological signature capable of distinguishing bacterial cellulitis from its mimics in clinical practice.

Improvement of CRB-65 as a prognostic tool in adult patients with community-acquired pneumonia.

BACKGROUND: Patients with community-acquired pneumonia (CAP) often require hospitalisation. CRB-65 is a simple and useful scoring system to predict mortality. However, prognostic factors such as underlying disease and blood oxygenation are not included despite their potential to increase the performance of CRB-65. METHODS: The study included 1172 consecutive patients (830 inpatients, 342 outpatients) with CAP. Mortality, sensitivity, specificity, positive predictive value and negative predictive value, and the area under the receiver operating characteristic (ROC) curve with 95% CI were calculated. Prognostic accuracy was evaluated after adding coexisting illnesses according to the Pneumonia Severity Index (malignancy, heart failure, hepatic, renal and cerebrovascular disease) and pulse oximetry (SpO2). RESULTS: Mean age was 65 years, 30-day mortality 7% (inpatients 9%, outpatients 1%). Addition of one point for the presence of ≥1 coexisting condition and one point for SpO2 <90% increased the area under the ROC curve of CRB-65 from 0.82 (95% CI 0.77 to 0.85) to 0.87 (95% CI 0.84 to 0.90; p<0.0001). CONCLUSIONS: Modification of CRB-65 by including hypoxaemia and presence of specified underlying diseases increased the scoring system's prognostic accuracy while retaining its independence of laboratory tests. DS CRB-65 may have the potential to further facilitate site of care decision for patients with CAP.