Bendamustine-induced nephrogenic diabetes insipidus - A case report.

INTRODUCTION: In patients with relapsed or refractory lymphoma, high-dose chemoimmunotherapy with subsequent autologous hematopoietic cell transplantation (HCT) is a standard of care. Bendamustine, an alkylating agent, is used in the BeEAM (bendamustine, etoposide, cytarabine, melphalan) protocol for conditioning therapy before autologous HCT in patients with relapsed or refractory lymphoma who are eligible for transplant. There is no consensus regarding an optimal salvage regimen and the approach varies according to toxicity. CASE REPORT: We present a case of partial nephrogenic diabetes insipidus after receiving bendamustine, as part of the BeEAM protocol.Management and outcome: The patient was managed with parenteral fluid administration and intranasal desmopressin before the condition resolved on its own. DISCUSSION: We summarize published reports of bendamustine-induced diabetes insipidus.

Amyloidogenicity of naturally occurring full-length animal IAPP variants.

The aggregation of the 37-amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic ß-islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on-path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full-length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full-length IAPP.

Access to heart failure care post emergency department visit: do we meet established benchmarks and does it matter?

BACKGROUND: The Canadian Cardiology Society recommends that patients should be seen within 2 weeks after an emergency department (ED) visit for heart failure (HF). We sought to investigate whether patients who had an ED visit for HF subsequently consult a physician within the current established benchmark, to explore factors related to physician consultation, and to examine whether delay in consultation is associated with adverse events (AEs) (death, hospitalization, or repeat ED visit). METHODS: Patients were recruited by nurses at 8 hospital EDs in Québec, Canada, and interviewed by telephone within 6 weeks of discharge and subsequently at 3 and 6 months. Clinical variables were extracted from medical charts by nurses. We used Cox regression in the analysis. RESULTS: We enrolled 410 patients (mean age 74.9 ± 11.1 years, 53% males) with a confirmed primary diagnosis of HF. Only 30% consulted with a physician within 2 weeks post-ED visit. By 4 weeks, 51% consulted a physician. Over the 6-month follow-up, 26% returned to the ED, 25% were hospitalized, and 9% died. Patients who were followed up within 4 weeks were more likely to be older and have higher education and a worse quality of life. Patients who consulted a physician within 4 weeks of ED discharge had a lower risk of AEs (hazard ratio 0.59, 95% CI 0.35-0.99). CONCLUSION: Prompt follow-up post-ED visit for HF is associated with lower risk for major AEs. Therefore, adherence to current HF guideline benchmarks for timely follow-up post-ED visit is crucial.

Comparison of Questionnaire and Performance-Based Physical Frailty Scales to Predict Survival and Health-Related Quality of Life in Patients With Heart Failure.

Background Frailty is prevalent in older adults with heart failure and is associated with poor outcomes; however, there remains uncertainty on how to measure frailty in clinical practice. Methods and Results A multicentric prospective cohort study was assembled at 4 heart failure clinics to compare the prognostic value of 3 physical frailty scales in ambulatory patients with heart failure. Outcomes were all-cause death or hospitalization and health-related quality of life using the 36-Item Short Form survey questionnaire (SF-36) at 3 months. Multivariable regression was adjusted for age, sex, Meta-Analysis Global Group in Chronic Heart Failure score, and baseline SF-36 score. The cohort included 215 patients (mean age 77.6 years). All 3 frailty scales were independently associated with death or hospitalization at 3 months; the adjusted odds ratios standardized per 1 SD worsening of the Short Physical Performance Battery; Fried, and strength, assistance with walking, rising from a chair, climbing stairs, and falls scales were 1.67 (95% CI, 1.09-2.55), 1.60 (95% CI, 1.04-2.46), and 1.55 (95% CI, 1.03-2.35), respectively, with C statistics of 0.77 to 0.78. All 3 frailty scales were independently associated with worsening SF-36 scores, especially the Short Physical Performance Battery, for which 1 SD worsening of frailty translated to a decrement of -5.86 (-8.55 to -3.17) and -5.51 (-7.82 to -3.21) points in the Physical Component Score and Mental Component Score. Conclusions All 3 physical frailty scales were associated with death, hospitalization, and reduced health-related quality of life in ambulatory patients with heart failure. Questionnaire or performance-based physical frailty scales can be used to offer prognostic value and a therapeutic target in this vulnerable population. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03887351.

Impact of Pharmacist-Provided Education Using New Information Sheets on Activation in Patients Treated with Oral Antineoplastic Drugs (IMPACT-OAD Project).

Background: Oral antineoplastic drugs (OADs) play an increasing role in the treatment of cancer. Patients must have a high degree of understanding and autonomy to manage the numerous adverse effects at home. In Quebec, recommendations have been made for oncology pharmacists to systematically counsel all patients who are starting an OAD. Objective: To measure the impact of education provided by oncology pharmacists on patient activation. Methods: In this prospective, single-centre, observational cohort study, patients starting an OAD received education from oncology pharmacists, who used the 2020 updated version of information sheets from the Groupe d'étude en oncologie du Québec (GEOQ, www.geoq.info). The Patient Activation Measure (PAM-13) questionnaire was used to measure patients' activation before and after the intervention. Results: Of the 43 patients recruited in the intention-to-treat analysis, 41 were included in the modified intention-to-treat analysis. The mean difference between PAM-13 scores before and after the intervention was 2.30 (standard deviation [SD] 11.85) (p = 0.22) in the intention-to-treat analysis and 3.63 (SD 10.33) (p = 0.032) in the modified intention-to-treat analysis; these differences were less than the 5 points required for a result to be considered clinically meaningful. None of the effect-modifying variables for which data were collected had a significant impact on the degree of activation; however, a weak negative correlation was observed between the level of health literacy and the change in PAM-13 score. Conclusions: The study did not show a clinically meaningful change in patient activation following pharmacist-provided education, according to the updated GEOQ information sheets. Further studies are needed to evaluate these data in a larger population and to determine whether the impact of education persists beyond the first treatment cycle.

Contexte: Les médicaments antinéoplasiques par voie orale (MAVO) occupent une place grandissante dans le traitement du cancer. Les patients doivent avoir un degré élevé de compréhension et d'autonomie pour gérer les nombreux effets indésirables à domicile. Au Québec, des recommandations ont été émises pour que les pharmaciens en oncologie conseillent systématiquement tous les patients qui débutent des MAVO. Objectif: Mesurer l'impact des enseignements effectués par les pharmaciens en oncologie sur l'activation du patient. Méthodes: Dans cette étude de cohorte prospective, monocentrique et observationnelle, les patients qui commençaient à prendre des MAVO ont reçu un enseignement effectué par un pharmacien en oncologie. Ceux-ci utilisaient les feuillets d'information pour les patients du Groupe d'étude en oncologie du Québec (GEOQ, www.geoq.info) mis à jour en 2020. Le questionnaire de Mesure d'activation du patient (MAP-13) a été utilisé pour mesurer l'activation des participants avant et après l'intervention. Résultats: Sur les 43 participants recrutés dans l'analyse en intention de traiter, 41 ont été inclus dans l'analyse en intention de traiter modifiée (mITT). La différence moyenne entre les scores MAP-13 avant et après était de 2,30 (écart type [SD] 11,85) (p = 0,22) dans l'analyse en intention de traiter et de 3,63 (SD 10,33) (p = 0,032) dans l'analyse mITT; ces différences étaient inférieures aux 5 points requis pour qu'un résultat soit considéré comme cliniquement significatif. Aucune des variables modificatrices d'effet pour lesquelles des données ont été recueillies n'a eu d'effet significatif sur le degré d'activation; cependant, une faible corrélation négative a été observée entre le niveau de littératie en santé et la variation du score MAP-13. Conclusions: L'étude n'a pas démontré de changement cliniquement significatif dans l'activation des patients à la suite de l'enseignement effectué par le pharmacien en oncologie sur la base des feuillets d'information actualisés du GEOQ. D'autres études sont nécessaires pour évaluer ces données chez une plus grande population et pour déterminer si l'impact de l'enseignement perdure au-delà du premier cycle de traitement.

Patient expectations from implantable defibrillators to prevent death in heart failure.

BACKGROUND: Indications for implantable cardioverter-defibrillators (ICDs) in heart failure (HF) are expanding and may include more than 1 million patients. This study examined patient expectations from ICDs for primary prevention of sudden death in HF. METHODS AND RESULTS: Study participants (n = 105) had an EF <35% and symptomatic HF, without history of ventricular tachycardia/fibrillation or syncope. Subjects completed a written survey about perceived ICD benefits, survival expectations, and circumstances under which they might deactivate defibrillation. Mean age was 58, LVEF 21%, 40% were New York Heart Association Class III-IV, and 65% already had a primary prevention ICD. Most patients anticipated more than10 years survival despite symptomatic HF. Nearly 54% expected an ICD to save >or=50 lives per 100 during 5 years. ICD recipients expressed more confidence that the device would save their own lives compared with those without an ICD (P < .001). Despite understanding the ease of deactivation, 70% of ICD recipients indicated they would keep the ICD on even if dying of cancer, 55% even if having daily shocks, and none would inactivate defibrillation even if suffering constant dyspnea at rest. CONCLUSIONS: HF patients anticipate long survival, overestimate survival benefits conferred by ICDs, and express reluctance to deactivate their devices even for end-stage disease.

Handheld echocardiography offers rapid assessment of clinical volume status.

BACKGROUND: Assessment of volume status is vital for successful management of patients in heart failure (HF) programs. Bedside determination of elevated left-sided filling pressure (LFP) can be challenging and frequently inaccurate; therefore, incorporating technology such as handheld echocardiography, to aid in estimation of LFP, may improve patient care. In this study, we evaluated the feasibility and accuracy of handheld echocardiography by a nonexpert for potential use in the point of care evaluation of compensation. METHODS: Subjects were recruited from the HF clinic or inpatient service at a single center. Each subject underwent a focused handheld transthoracic echocardiogram by a medical resident trained for 10 hours. Subjects were assigned to 1 of 4 filling patterns (1 = normal, 2 = abnormal relaxation, 3 = pseudonormal, 4 = restrictive) based on measurements by pulsed wave and tissue Doppler. A 3-step echocardiography test for congestion in HF (TEC-HF) was devised for estimation of LFP. The gold standard for determining elevated LFP was clinical evaluation by a HF specialist, who classified subjects as being euvolemic or hypervolemic. RESULTS: A total of 100 consecutive subjects (72% male) were recruited, with average age of 60 years and left ventricular ejection fraction of 27%. All subjects had evaluable echocardiographic data. Based on TEC-HF, filling patterns 3 and 4 predicted hypervolemia and patterns 1 and 2 predicted euvolemia, with sensitivity and specificity of 86% and 92%, respectively, and positive and negative predictive values of 86% and 92%, respectively. CONCLUSIONS: Applying TEC-HF with handheld echocardiography accurately reflects clinical LFP as assessed by HF specialists. This procedure was easily taught to nonexpert medical staff who obtained adequate images in all patients. Handheld echocardiography could be a useful tool for assessing volume status in nonspecialized community settings.

Lack of long-term benefits of a 6-month heart failure disease management program.

BACKGROUND: Heart failure (HF) represents a major burden on the health care system, causing repeated hospitalizations and numerous emergency department (ED) visits. In a 6-month randomized study of a multidisciplinary HF clinic, we have previously shown decreased hospital readmissions and improved quality of life. Despite these encouraging results, it is unknown if these beneficial effects are sustained. METHODS AND RESULTS: To assess long-term recurrent ED visits, readmissions, and mortality among HF patients who were discharged after a 6-month intensive HF management program (HFMP). Of the 230 subjects (New York Heart Association Class II-IV) who were initially randomized to standard follow-up care or to a HFMP for 6 months, 190 were studied retrospectively for long-term evaluation. Long-term data was obtained from the Quebec administrative health databases. We compared the intervention and control groups for the number of recurrent ED visits, hospital readmissions, and all-cause deaths. After a mean follow-up of 2.8 +/- 1.7 years, there was no difference in the composite end point of all-cause death, hospital admissions, and ED visits between those patients initially in the HFMP group and the controls. After multivariable adjustment, there was no difference in the composite primary endpoint (HR 1.01, 95% CI: 0.75-1.37) or in the secondary end point of all-cause death alone (HR 1.09, 95%CI:0.69-1.72) between those initially assigned to the HF clinic and those receiving usual care. CONCLUSIONS: For severely ill patients, the clinical and resource benefits of a 6-month HFMP are not sustained upon program cessation. Further research into the benefits of long-term HFMP is required.

Tricuspid regurgitation after cardiac transplantation: how many biopsies are too many?

BACKGROUND: Tricuspid regurgitation (TR) is common in patients after orthotopic cardiac transplantation (OHT). Endomyocardial biopsy (EMB) used to monitor for rejection may be a cause of TR. The purpose of this study was to identify a correlation between the severity of TR and the number of EMBs. METHODS: We studied 101 patients with OHT at our institution between May 1987 and August 2001. The number of EMBs performed in each patient was determined. Data on technique of anastomosis, liver and renal function, ejection fraction, and pulmonary artery pressure were also extracted. Echocardiography reports were reviewed to determine the presence and severity of TR. Symptoms of right heart failure were assessed by the amount of diuretic intake. RESULTS: Twenty-five (25%) of 101 patients had evidence of severe TR, whereas 76 (75%) had non-severe TR. Multivariate analysis identified EMB as the only independent predictor of the severity of TR (p < 0.0001). At last follow-up, 60% of patients with more than 31 EMBs had developed severe TR, whereas none of the patients with less than 18 EMBs had severe TR. Of the 25 patients who had severe TR, 15 (61%) needed high doses of daily diuretics, and 4 (16%) required tricuspid valve replacement. CONCLUSIONS: The development of TR after OHT is in large part due to EMBs used to monitor for rejection. There is a direct correlation between the number of EMBs and the severity of TR. We suggest a cutoff of less than 31 EMBs to reduce the risk of severe TR.

Computerized interpretation of the prehospital electrocardiogram: predictive value for ST segment elevation myocardial infarction and impact on on-scene time.

INTRODUCTION: Computerized interpretation of the prehospital electrocardiogram (ECG) is increasingly being used in the basic life support (BLS) ambulance setting to reduce delays to treatment for patients suspected of ST segment elevation myocardial infarction (STEMI). OBJECTIVES: To estimate 1) predictive values of computerized prehospital 12-lead ECG interpretation for STEMI and 2) additional on-scene time for 12-lead ECG acquisition. METHODS: Over a 2-year period, 1,247 ECGs acquired by primary care paramedics for suspected STEMI were collected. ECGs were interpreted in real time by the GE-Marquette 12SL ECG analysis program. Predictive values were estimated with a bayesian latent class model incorporating the computerized ECG interpretations, consensus ECG interpretations by study cardiologists, and hospital diagnosis. On-scene time was compared for ambulance-transported patients with (n  =  985) and without (n  =  5,056) prehospital ECGs who received prehospital aspirin and/or nitroglycerin. RESULTS: The computer's positive and negative predictive values for STEMI were 74.0% (95% credible interval [CrI] 69.6-75.6) and 98.1% (95% CrI 97.8-98.4), respectively. The sensitivity and specificity were 69.2% (95% CrI 59.0-78.5) and 98.9% (95% CrI 98.1-99.4), respectively. Prehospital ECGs were associated with a mean increase in on-scene time of 5.9 minutes (95% confidence interval 5.5-6.3). CONCLUSIONS: The predictive values of the computerized prehospital ECG interpretation appear to be adequate for diversion programs that direct patients with a positive result to hospitals with angioplasty facilities. The estimated 26.0% chance that a positive interpretation is false is likely too high for activation of a catheterization laboratory from the field. Acquiring prehospital ECGs does not substantially increase on-scene time in the BLS setting.

Gender and other disparities in referral to specialized heart failure clinics following emergency department visits.

BACKGROUND: Persons with heart failure (HF) at high risk for adverse events should be followed by specialized HF clinics, since follow-up by specialized HF clinics improves outcomes for HF patients. The objective was to determine whether there were disparities for gender and other factors associated with referral of patients to specialized HF clinics. METHODS: In this prospective cohort study, patients with a confirmed primary diagnosis of HF were recruited by nurses at 8 hospital emergency departments (ED) in Québec, Canada. They were interviewed by telephone at 6 weeks post ED discharge and subsequently at 3 months and 6 months. Pertinent clinical variables were extracted from medical charts by trained nurses. Bivariate analysis and multiple logistic regression were used to identify whether gender and other potential factors were associated with referral to the HF clinic. RESULTS: We enrolled 549 patients (mean age 75.5±11.0 years; 51% males). By 6 months after their ED visit for HF, 37.6% of the cohort were referred to specialized HF clinics. Men were more likely to be referred (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.12, 3.74). Other factors associated with referral were younger age (OR 0.95; 95% CI 0.92, 0.98), and systolic dysfunction HF (left ventricle ejection fraction <40%) (OR 3.08; 95% CI 1.77, 5.46). CONCLUSION: There are disparities in referral with respect to gender, age, and type of HF. These disparities in referral need to be addressed.

Predictive values of the electrocardiogram in diagnosing pulmonary hypertension.

OBJECTIVE: Determination of the prevalences and predictive values of specific electrocardiograms (ECG) criteria of right ventricular hypertrophy (RVH) or right atrial enlargement for pulmonary hypertension. METHODS: We examined the ECG and trans-thoracic echocardiograms (TTE) of 372 patients who had TTE and 12-lead ECG, performed within 24 h interval, during a 12-month period. There were 282 consecutive adults with pulmonary hypertension (pulmonary artery systolic pressure (PASP) >30 mm Hg) and 90 subjects with normal cardiac anatomy and normal PASP. The mean age of patients with pulmonary hypertension was 74.0+/-11.0 years and 66% of them were females. The control subjects had a mean age of 56.3+/-17.5 years and 58.8% were females. RESULTS: ECG patterns focusing on the R and S amplitudes and R/S ratio in V1 were more predictive of pulmonary hypertension than ECG patterns involving leads V5 and V6. In particular, each of the following ECG patterns had good positive predictive values for pulmonary hypertension (greater than 80%): R in I less than 2 mm+S in V1/=60 mm Hg). Electrocardiographic criterion for right atrial enlargement was not found in any of the patients with pulmonary hypertension. CONCLUSIONS: ECG criteria of RVH were rare in patients with pulmonary hypertension. ECG patterns focusing on the R and S amplitude in V1 and right axis deviation with QRS axis deviation>/=110 degrees had excellent positive predictive values of pulmonary hypertension. However, the absence of ECG criteria of RVH could not exclude with certainty the presence of pulmonary hypertension.