Large Cohort Of Unselected Patients Research Articles

Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery.

Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports. Multinational observation series to evaluate the pragmatic "real-life" application of tPA/DNase treatment for pleural infection in a large cohort of unselected patients. All patients from eight centers who received intrapleural tPA/DNase for pleural infection between January 2010 and September 2013 were included. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity and inflammatory markers, need for surgery, and adverse events. Of 107 patients treated, the majority (92.3%) were successfully managed without the need for surgical intervention. No patients died as a result of pleural infection. Most patients (84%) received tPA/DNase more than 24 hours after failing to respond to initial conservative management with antibiotics and thoracostomy. tPA/DNase increased fluid drained from a median of 250 ml (interquartile range [IQR], 100-654) in the 24 hours preceding commencement of intrapleural therapy to 2,475 ml (IQR 1,800-3,585) in the 72 hours following treatment initiation (P < 0.05). We observed a corresponding clearance of pleural opacity on chest radiographs from a median of 35% (IQR 25-31) to 14% (7-28) of the hemithorax (P < 0.001), as well as significant reduction in C-reactive protein (P < 0.05). Pain necessitating escalation of analgesia occurred in 19.6% patients, and nonfatal bleeding occurred in 1.8%. This large series of patients who received intrapleural tPA/DNase therapy provides important evidence that the treatment is effective and safe, especially as a "rescue therapy" in patients who do not initially respond to antibiotics and thoracostomy drainage.

TYPE 2 MI IN SOUTHERN ALBERTA: A DESCRIPTIVE ANALYSIS

The concept of type 2 myocardial infarction (MI), or myocardial necrosis due to supply-demand mismatch, was introduced in 2007, causing contention and confusion for many clinicians. We aimed to gather data on a large, unselected population of patients with type 2 MI and to evaluate investigation, management and prognosis. All patients with a positive troponin over a 2-year period in the Calgary Health Region were identified. Chart review was performed and patients with explicit ACS diagnoses excluded, leaving only patients with troponin elevations presumably associated with type 2 MI. Follow up data were obtained through the use of the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) database and its linkage to the Alberta Bureau of Vital Statistics. From January 1, 2007 to December 31, 2008, 998 patients with a presumptive diagnosis of type 2 MI were identified, with the majority admitted to general practice or internal medicine services. Infrequent symptoms were recorded, with the most common symptom being shortness of breath. Despite the troponin elevation, ECG was not performed in 6%, and 1/3 did not have subsequent ECGs after an initial assessment. The most common ECG change identified was T wave changes (24.1%), with ST depression in 13.7% and ST elevation observed in 5.6% of diagnosed type 2 MI. Echocardiograms were performed in only 23.2%, CT PE in 6.2%, and nuclear myocardial perfusion imaging in 0.05%. No patient underwent cardiac catheterization. Evidence-based therapy was prescribed infrequently, with only 25.5% given ASA and 16.7% statin. Outcomes were poor, as demonstrated in the Table. Readmission rates were high at 13.5% at 30-days and 35.2% at 1-year. In this large unselected cohort of patients with presumptive diagnoses of type 2 MI, ECG changes were common, and investigations to rule out type 1 MI or ongoing underlying ischemia were uncommon. Outcomes for these patients were poor and readmission rates high. Further research is required to determine appropriate management of this important group of patients.

IMPACT OF PROVINCIAL GUIDELINE IMPLEMENTATION ON UTILIZATION OF EVIDENCE-BASED THERAPY FOLLOWING ACUTE ST ELEVATION MYOCARDIAL INFARCTION - ANALYSIS FROM THE CARDIOVASCULAR HEALTH NOVA SCOTIA DATABASE

demonstrated in the Table. Readmission rates were high at 13.5% at 30-days and 35.2% at 1-year. CONCLUSION: In this large unselected cohort of patients with presumptive diagnoses of type 2MI, ECG changes were common, and investigations to rule out type 1 MI or ongoing underlying ischemia were uncommon.Outcomes for these patients were poor and readmission rates high. Further research is required to determine appropriatemanagement of this important group of patients.

Echocardiographic assessment of right ventricular systolic function in a population of unselected patients before cardiac surgery: A multiparametric approach is necessary

According to recent USA guidelines, right ventricular (RV) dysfunction can be diagnosed on the basis of a single parameter, such as tricuspid lateral annular systolic velocity (S')<10 cm/s or RV fractional area change (RVFAC)<35%. To assess these recommendations in a large unselected cohort of patients awaiting cardiac surgery and evaluate less validated RV function criteria. Among the consecutive patients, 413 were prospectively enrolled and underwent comprehensive echocardiography, including S', RVFAC and other RV parameters (right myocardial performance index; acceleration time, isovolumic velocity and isovolumic acceleration [IVA]; RV dP/dt; isovolumic relaxation time; two-dimensional [2D] strain). We defined subgroups of highly probable RV dysfunction (S'<10 cm/s and RVFAC<35%) and highly probable normal RV function (S'≥10 cm/s and RVFAC≥35%) as reference groups. Indices of preload and afterload were also recorded. Of 413 patients, 320 (77.5%) had normal RV function. In 93 patients, S' and/or RVFAC were abnormal; both were abnormal in 39 (42%) patients. Using our reference groups, IVA≤1.8 m/s2 and basal 2D strain≥-17% were of most value in diagnosing RV dysfunction. IVA was least load dependent while basal 2D strain appeared to be afterload and preload dependent. In this large population, S' and RVFAC were sometimes discrepant, supporting the need for a multiparametric approach when evaluating RV function. Among seven less validated criteria, IVA and 2D strain had the best diagnostic value. Unlike 2D strain, IVA was not influenced by loading conditions.

The prevalence and outcomes of transradial percutaneous coronary intervention for acute coronary syndrome. Analysis from the single-centre ISACS-TC Registry (International Survey of Acute Coronary Syndrome in Transitional Countries) (2010-12)

The aims were to compare the prevalence and short-term outcomes of transradial (TRA) percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) in dedicated radial centre. This was a single-centre observational study of 3484 consecutively enrolled patients with ACS in a 3-year period (2010–12). There were 1648 patients with ST-elevation myocardial infarction (STEMI) and 1836 with non-ST-elevation ACS (NSTEACS). All patients underwent diagnostic coronary angiography within 24 h (STEMI) or within 72 h (NSTEACS). Percutaneous coronary intervention was performed in 84.9% patients (96.6% with STEMI and 74.9% with NSTEACS). Optimal medical treatment (OMT) only was recommended to 2.2% with STEMI and to 11.1% with NSTEACS. Coronary artery bypass graft (CABG) surgery was performed for 1.7% of STEMI and 14.1% of patients with NSTEACS ( P < 0.0001). Most of the PCI procedures were performed through the wrist access (radial 97% and ulnar artery access 1.3%). There was high overall procedural success 98.5% (STEMI 99% and NSTEACS 97%). At 30 days, cardiovascular mortality was 4.7% in STEMI patients and 1.4% in patients with NSTEACS who were treated by PCI ( P < 0.0001). Major adverse cardiac events defined as a composite of death, myocardial infarction, stroke, and non-CABG major bleeding and major access site complications at 30 days were higher in STEMI vs. NSTEACS patients (7.7 vs. 4.4%; P < 0.0001). Transradial access for PCI in a large cohort of unselected patients with ACS, is safe and feasible when performed by experienced radial operators. Patients with NSTEACS are more frequently treated with OMT and have higher referral rate to CABG in comparison with STEMI patients. There is higher 30 day mortality in patients with STEMI.

Risk of Stent Thrombosis Among Bare-Metal Stents, First-Generation Drug-Eluting Stents, and Second-Generation Drug-Eluting Stents: Results From a Registry of 18,334 Patients

This study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years. In patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations. A total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3groups according to treatment with BMS, G1-DES, and G2-DES. The cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47to 2.86; p < 0.001). G2-DES were associated with a similar risk of stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p= 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p < 0.001), but not with G2-DES compared with BMS (OR: 1.01; 95% CI: 0.32 to 3.25; p= 0.98). In a large cohort of unselected patients undergoing coronary stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS.

Venous Thromboembolism Risk in Patients With Cancer Receiving Chemotherapy: A Real-World Analysis

The occurrence of malignant disease increases the risk for venous thromboembolism (VTE). Here we evaluate the risk for VTE in a large unselected cohort of patients with cancer receiving chemotherapy. The United States IMPACT health care claims database was retrospectively analyzed to identify patients with a range of solid tumors who started chemotherapy from January 2005 through December 2008. International Classification of Diseases, 9th revision, Clinical Modification Codes were used to identify cancer location, presence of VTE 3.5 months and 12 months after starting chemotherapy, and incidence of major bleeding complications. Health care costs were assessed one year before initiation of chemotherapy and one year after initiation of chemotherapy. The overall incidence of VTE 3.5 months after starting chemotherapy was 7.3% (range 4.6%-11.6% across cancer locations) rising to 13.5% at 12 months (range 9.8%-21.3%). The highest VTE risk was identified in patients with pancreatic, stomach, and lung cancer. Patients in whom VTE developed had a higher risk for major bleeding at 3.5 months and at 12 months (11.0% and 19.8% vs. 3.8% and 9.6%, respectively). Health care costs were significantly higher in patients in whom VTE developed. Those undergoing chemotherapy as outpatients are at increased risk for VTE and for major bleeding complications. Thromboprophylaxis may be considered for such patients after carefully assessing the risks and benefits of treatment.

Effect of cerebrovascular disease on long-term outcome of patients with acute coronary syndromes: findings from a large cohort of unselected patients

Effect of cerebrovascular disease on long-term outcome of patients with acute coronary syndromes: findings from a large cohort of unselected patients

Osteoradionecrosis: Patient characteristics and treatment outcome in a cohort from Copenhagen University Hospital 1995-2005

Purpose: The present retrospective observational study was undertaken to evaluate disease characteristics, treatment strategy and treatment results of a large unselected cohort of patients with osteoradionecrosis (ORN) after radiation therapy (RT) for head and neck cancer at the Copenhagen University Hospital 1995-2005. Patients and Methods: Medical records of 180 consecutive patients diagnosed with ORN were reviewed. Patients had all received treatment for ORN at the Department of Oral Maxillofacial Surgery, Copenhagen University Hospital from 1 January 1995 to 31 December 2005. Only patients who had received their primary treatment for head and neck cancer in the eastern part of Denmark were included. Results: The cohort consisted predominantly of men (78%) of whom a clear majority were smokers (60.6%). The median age was 57. The median time until the onset of post-RT ORN was 1.9 years. ORN lesions were mostly located in the mandibular symphysis, body and angle regions. Hyperbaric oxygen treatment was given to 93% of the patients; and 25% of the patients completed disease-free follow-up after a median of 1.2 years. At the time of study termination, 17% were still undergoing active treatment. Social class distribution showed a clear predominance of the lower social classes. Conclusion: The present study demonstrates the variability of mandibular ORN. Onset varies greatly, which demonstrates the lifelong nature of the risk of ORN. In the majority of patients, the primary tumor was located in the oral cavity or the oropharynx. ORN does not appear to imply social inequality.

Mechanism and causes of failed transradial approach — our experience

Background: The transradial approach (TRA) for percutaneous coronary diagnostic and interventional procedures has been shown to decrease vascular complications and improve clinical outcomes compared with transfemoral approach (TFA). Despite its obvious advantages, TRA is still infrequently used in routine practice. Main disadvantages of TRA compared with TFA, beside the necessary learning curve is a variable rate of transradial failure due to specific problems related to this arterial access. Objective: To evaluate the incidence and causes of TRA failure in coronary angiographies and interventional procedures performed in a large cohort of unselected patients in single center observational study. Methods: All consecutive right TRA procedures performed at our institution between January 2011 and December 2012, by low-to-intermediate volume operators, were analyzed retrospectively. Results: In the observed period we performed 1341 coronary diagnostic and interventional procedures, 1243 (92,7%) were performed using right TRA as primary access. Mean age was 64.1 years, and 35% were female. TRA failure occurred in 75 procedures (6.0%). In that subgroup, mean age was 68.3 and 61% were female. Two main causes of failed TRA were puncture failure in 32 (42.6%) and unsuitable anatomy (i.e. tortuous subclavian and brachiocephalic arteries, radial loop, radial hypoplasia or abberant arteries) in 31 (41.3%) patients. The remaining causes occurred at a much lower frequency: impassable radial spasm in 7 (9.3%), technical difficulty in 3 (4.0%) and vascular complications in 2 (2.6%) cases. The procedure was successfully completed in all 75 (100%) patients with TRA failure by switching to TFA. Conclusions: TRA coronary procedures, even in acute coronary syndrome settings, can be performed in the intermediate volume center by low-to-intermediate volume operators, using standard and dedicated equipment with a low failure rate. Older age and female sex are predictors of TRA failure.

Prevalence of primary hyperparathyroidism among patients with low bone mass

Accelerated rate of bone turnover and increased resorption due to primary hyperparathyroidism (PHPT) result in osteopenia and an increase in the fracture risk. However, there are no data about the relative frequency of the PHPT in the subpopulation with the low bone mass. The aim of the study was to evaluate the diagnostic power of the bone densitometry in diagnosis of PHPT. Material consisted of 4016 new patients: 2504 women and 1512 men. Bone mineral density (BMD) in the L2 - L4 vertebra and femoral neck was measured by DEXA (LUNAR - DPX or LUNAR - EXPERT, Lunar Radiation Corp., USA). All the patients with BMD Z-score below -2.0 SD (according to the sex and age) were the subjects of further diagnostic procedures. The serum calcium and intact PTH level as well as 24-hours urine excretion was measured. In 451 (331 women and 120 men) out of the total 4016 patients, the measured BMD Z-scores were below -2.0 SD. Out of these 451 patients, 52 were diagnosed with PHPT. In 41 patients, diagnosis of PHPT was based on elevated serum intact PTH in the face of overt hypercalcemia. The remaining 11 normocalcemic patients with elevated PTH and coexisting vitamin D deficiency, will become hypercalcemic after vitamin D replacement. In the large cohort of unselected patients who presented for bone densitometry, a very high (11.5%) prevalence of PHPT was found among subjects with low bone mass (BMD Z-score less than -2.0 SD). Presented results confirm the importance of the BMD measurements in the screening of the disease.

Reduced Risk of Death with Warfarin – Results of an Observational Nationwide Study of 20 442 Patients with Atrial Fibrillation and Ischaemic Stroke

Warfarin is demonstrated to be superior in efficacy over antiplatelet agents for the prevention of stroke, but the relationship between warfarin and mortality is less clear. Our aim was to investigate this relationship in a large cohort of unselected patients with atrial fibrillation and ischaemic stroke. This observational study was based on patients who were discharged alive and registered in the Swedish Stroke Register in 2001 through 2005. Vital status was retrieved by linkage to the Swedish Cause of Death Register. We calculated a propensity score for the likelihood of warfarin prescription at discharge from hospital. The risk of death and 95% confidence intervals were estimated in Cox regression models. Out of the 20 442 patients with atrial fibrillation and ischaemic stroke (mean age = 79·5 years), 31% (n = 6399) were prescribed warfarin. After adjustment for the propensity score, warfarin was associated with a reduced risk of death (0·67; 95% confidence interval, 0·63-0·71). The crude rate (per 100 person-years) of fatal non-haemorrhagic stroke was lower in patients who received warfarin (1·60; 95% confidence interval, 1·34-1·89) compared to those who received antiplatelet (6·83; 95% confidence interval, 6·42-7·25). The rates (per 100 person-years) of fatal haemorrhagic stroke were 0·21 (95% confidence interval, 0·12-0·32) and 0·43 (95% confidence interval, 0·34-0·55) in patients prescribed warfarin and antiplatelet therapy, respectively. In addition to its established benefit for stroke prevention, warfarin therapy in patients with atrial fibrillation and ischaemic stroke was associated with a reduced risk of death, without an increased risk of fatal haemorrhagic stroke.

Comorbidities and the quality of life in hypertensive patients

An important factor influencing the perception of health‑related quality of life (HRQoL) is the presence of chronic diseases, especially polymorbidity. However, little is known about how concurrent chronic diseases influence the HRQoL of hypertensive patients. The primary aim of the study was to assess the relationship between comorbidities and different aspects of HRQoL in a large unselected cohort of patients undergoing treatment for hypertension. A questionnaire‑based study was conducted by 832 primary care physicians in a group of 12,525 unselected patients treated for hypertension for at least 3 months. HRQoL was evaluated using the Medical Outcomes Study 12‑item Short‑Form Health Survey (SF‑12). Coexisting diseases were reported in 7986 patients (63.8%). Significantly lower HRQoL values were associated with coexisting diseases, especially obstructive respiratory disease, degenerative disc disease, radiculopathy, coronary artery disease, heart failure, stroke, diabetes, epilepsy, neurotic disorders, and mood disorders. The HRQoL of hypertensive patients decreased significantly with age and duration of antihypertensive therapy (>2 years). HRQoL values were higher for men and participants with higher education and lower for participants who were obese or had visceral obesity. Antihypertensive therapy was effective in 25.4% of the participants. Chronic diseases concomitant with arterial hypertension negatively affect all dimensions of the HRQoL.

A unifying diagnosis for pancytopenia, fever, hypoglycemia, and lactic acidosis

A unifying diagnosis for pancytopenia, fever, hypoglycemia, and lactic acidosis

Antral Follicle Counts Are Strongly Associated With Live Birth Rates After Assisted Reproduction, With Superior Treatment Outcome in Women With Polycystic Ovaries

Objective: To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients coveri ...

Diagnostic accuracy of quantitative heart-fatty acid binding protein assays compared with Cardiodetect ® in the early detection of acute coronary syndrome

Heart-fatty acid binding protein (h-FABP) has been proposed as a cardiac marker for the early detection of acute coronary syndrome (ACS). In a study of 677 patients admitted to the emergency department (ED) for chest pain, we found that a semiquantitative point-of-care test that detects h-FABP (Cardiodetect(®)) had low sensitivity for the prediction of ACS. The aim of this ancillary study was to analyze and compare the performance of h-FABP for early ACS diagnosis in this large cohort of unselected patients, using a quantitative immunoassay and Cardiodetect(®). h-FABP was measured with a ready-to-use, solid-phase, enzyme-linked immunosorbent assay (ELISA) in 677 patients admitted to the ED with chest pain and suspected non-ST-segment elevation ACS. Two physicians, blinded to the results of the marker, categorized patients as having or not having non-ST-segment elevation ACS. Non-ST-segment elevation ACS was diagnosed in 185 patients (27.3%). The median h-FABP level was higher in patients with ACS (1.36μg/L, interquartile range [IQR] 0.59-3.55) than in those without ACS (0.58μg/L, IQR 0.24-1.34; P<0.01). The area under the curve was 0.68 (95% confidence interval [CI] 0.63-0.73). h-FABP did not improve the performance of a model that included the usual diagnostic tools for ACS management (odds ratio 0.92, 95% CI 0.32-2.70). The classification agreement between the ELISA and Cardiodetect(®) was 92.1% (kappa 0.39). In this study, we confirmed that measurement of h-FABP was insufficient to be used as a marker of ACS and NSTEMI in ED, whatever the analytical technique used.

Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries

To evaluate the association of antral follicle count (AFC) with invitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Prospective observational study. University-affiliated private infertility center. 2,092 women undergoing 4,308 IVF-ICSI cycles. AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Pregnancy rate, live-birth rate, and stimulation outcome parameters. The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC ∼30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity.

One‐year clinical outcome in an unselected patient population treated with the Genous™ endothelial progenitor cell capturing stent

We assessed the 1-year clinical outcome in a large cohort of unselected patients treated with an endothelial progenitor cell (EPC) capturing coronary stent. The novel EPC capturing stent is coated with CD34+ antibodies that bind circulating EPCs to the stent surface, thereby accelerating endothelialization of the stent struts; it is hypothesized that this may prevent restenosis and stent thrombosis. A total of 405 unselected patients were treated percutaneously with the EPC capturing stent. The majority of patients had complex lesions with an estimated high risk of restenosis. The primary endpoint defined as the composite of cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) at 1-year was 13.3%, mainly attributable to TLR which was 10.9%. The occurrence of definite and probable ST was low, 0.5 and 0.7%, respectively. Based on the risk of restenosis, in patients with an estimated high risk of restenosis (n = 249), the composite primary endpoint was 16.1% versus 9.0% in patients with an estimated low risk (n = 155). Moreover, the 1 year clinical outcomes in diabetic patient compared well with the nondiabetic patients. In this single-center study, the 1-year clinical follow-up in a "real-world" population treated with the EPC capturing stent showed good results. Currently, large randomized studies are conducted to evaluate the long-term safety and efficacy of this stent.

Thirty-day mortality of Clostridium difficile infection in a UK National Health Service Foundation Trust between 2002 and 2008

Few standardised data are available on mortality rates in patients with Clostridium difficile infection (CDI). The literature often reports 'attributable' mortality or cannot be universally applied. We aimed to investigate the pattern and trends in all-cause mortality in a large unselected cohort of patients affected by CDI. This was done by means of a retrospective cohort study between 2002 and 2008 of all patients with positive stool toxin tests indicating CDI in one National Health Service (NHS) Trust, comprising three general hospitals and seven community hospitals. Vital status of the patients was determined from two sources. In total, 2571 patients with a first episode of CDI were identified (1638 females; median age 82.1 years). Cumulative mortality at 7 days, 14 days, 30 days and 1 year was 13.4%, 20.8%, 32.5% and 58.7%, respectively. There was no significant difference in mortality between sex, year of diagnosis or hospital site. Mortality at 30 days increased incrementally from 3.4% in those aged <40 years to 41% in those >90 years. Mortality rates were significantly higher than reported by previous studies but were remarkably consistent over the time period and between different hospitals within the Trust. Prognosis falls with increasing age, and the age of this cohort may explain the high 30-day absolute mortality. CDI infection is associated with high early mortality. To reduce mortality, new interventions need to be introduced soon after diagnosis. There is a need for standardised outcome data for CDI.

Imatinib In Very Elderly CML Patients: What Can We Achieve?.

AbstractAbstract 1229In the “real world” of clinical practice, many very elderly CML patients have been treated with imatinib (IM), but there are few data on the results and the best initial dosage in such patients. To highlight peculiar aspects of toxicity and efficacy of IM in this subset which accounts for at least 10–15% of all CML cases, we retrospectively revised 156 CML patients in chronic phase treated with IM when aged > 75 years from 23 haematological Institutions in Italy; there were 85 males and 71 females, median age at IM start was 78.4 years (IR 76.1 – 81.4), Sokal Risk at diagnosis was low in 2 patients, intermediate in 90, high in 50 and not evaluable in 14. One or more concomitant diseases requiring specific treatments were present in 144/156 patients (92.3%), with 94 patients (60.2%) assuming 3 or more concomitant drugs. Thirty patients (19.2%) were in late chronic phase (≥ 12 months from diagnosis) and pretreated (25 with HU and 5 with IFN) before starting IM; on the whole, median time from diagnosis to IM was 1.2 months (IR 0.5 – 3.6). Starting dose of IM was 400 mg/day in 117 patients (75.0%) and 300 mg/day or less in 39 patients (25.0%); overall, 59 patients (37.8%) (52/117 at 400 mg starting dose and 7/39 at 3 300 mg starting dose) needed a dose reduction and 18 (11.5%) discontinued IM for toxicity (early toxicity in 13 and late toxicity in 5). Excluding the 13 patients who discontinued IM due to early toxicity, maximum tolerated daily dose during treatment was 400 mg in 63 patients, 300 mg in 51 patients and < 300 mg in 29 patients. According to CTC-AE, grade 3 – 4 hematological and extra-hematological toxicities were observed in 34 (21.7%) and 34 (21.7%) patients, respectively; 5 patients (3.2%) presented a pleural effusion during IM treatment. After a median treatment period of 29.4 months (IR 7.9 – 54.4), 8 patients (5.1%) are still too early (< 6 months of treatment), 13 (8.3%) discontinued IM due to early toxicity, 3 (1.9%) were resistant and 1 (0.7%) died from unrelated cause early after IM initiation: the remaining 131 patients (84.6%) achieved a complete haematological response (CHR). Among these 131 patients in CHR, 11 refused any other karyotipic or molecular evaluation (1 lost CHR and shifted to hydroxyurea, 4 are still alive in CHR, 6 died in CHR from unrelated causes), 17 achieved CHR only and 103 (66.0% of all 156 patients) achieved a cytogenetic response (CyR), which was major in 11 patients and complete (CCyR) in 92 (58.9% of all 156 patients). In addition, among the 92 patients in CCyR, 62 (39.7% of all 156 patients) achieved a molecular response (major molecular response in 40 patients and complete molecular response with an undetectable BCR/ABL hybrid gene at qualitative nested PCR in 22 patients). After a median follow-up of 34.0 months (IR 12.9 – 60.0), 36 patients have died (5 from disease progression and 31 from unrelated causes), 4 patients were lost to follow-up and 116 are still alive: 2-year and 4-year overall survival were 90.2% (CI95% 84.8 – 95.6) and 76.8% (CI95% 68.6 – 85.0), respectively. In conclusion, results from this large unselected cohort of patients show that should be definitely considered unethical to avoid IM therapy to any elderly patient; no upper age limit should be given but also very elderly (and with concomitant severe diseases) patients should have this chance of cure. The role of a reduced starting dose of IM warrants further studies. Disclosures:No relevant conflicts of interest to declare.