Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

PubMed

Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

2018-04-27

Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

Top-down approach is possible strategy for predicting breakthrough fUTIs and renal scars in infants.

PubMed

Kawai, Shina; Kanai, Takahiro; Hyuga, Taiju; Nakamura, Shigeru; Aoyagi, Jun; Ito, Takane; Saito, Takashi; Odaka, Jun; Furukawa, Rieko; Aihara, Toshinori; Nakai, Hideo

2017-07-01

Acute-phase technetium-99 m dimercaptosuccinic acid (DMSA) scintigraphy is recommended for initial imaging in children with febrile urinary tract infection (fUTI). Recently, the importance of identifying patients at risk of recurrent fUTI (r-fUTI) has been emphasized. To clarify the effectiveness of DMSA scintigraphy for predicting r-fUTI in infants, we investigated the relationship between defects on DMSA scintigraphy and r-fUTI. Seventy-nine consecutive infants (male: female, 60:19) with fUTI were enrolled in this study. DMSA scintigraphy was performed in the acute phase, and patients with defect underwent voiding cystourethrography and chronic-phase (6 months later) DMSA scintigraphy. Patients were followed on continuous antibiotic prophylaxis (CAP). Defects on acute-phase DMSA scintigraphy were observed in 32 children (40.5%) of 79. The mean follow-up observation period was 17.0 ± 10.1 months. Four patients had r-fUTI (5%). Two of them had defects on DMSA scintigraphy in both the acute phase and chronic phase, and had bilateral vesicoureteral reflux (VUR) grade IV. Two others had r-fUTI without defects on DMSA and did not have VUR. Twelve patients had defect on chronic-phase DMSA scintigraphy and four of them had no VUR. The top-down approach is a possible method for predicting r-fUTI in infants and does not miss clinically significant VUR. Also, given that the prevalence of r-fUTI was 5% regardless of the presence of defects on acute-phase DMSA, then, in conjunction with genital hygiene and CAP, acute-phase DMSA might be unnecessary if chronic-phase DMSA is performed for all patients to detect renal scar. © 2017 Japan Pediatric Society.

Nitrogen balance in patients with hemiparetic stroke during the subacute rehabilitation phase.

PubMed

Wada, A; Kawakami, M; Otsuka, T; Aoki, H; Anzai, A; Yamada, Y; Liu, F; Otaka, E; Akaboshi, K; Liu, M

2017-06-01

In highly invasive diseases, metabolism commonly changes. Hypercatabolism is frequent in acute stroke, and nitrogen balance tends to be negative. However, there has been no study describing nitrogen balance in subacute and chronic stroke patients. The present study aimed to examine nitrogen balance in the subacute and chronic phases and to identify the factors related to it. Nitrogen balance was calculated from the collected urine of 56 patients with subacute stroke [mean (SD) 53.8 (18.4) days post-stroke] who were admitted for rehabilitation for their first-ever ischaemic or nonsurgical haemorrhagic stroke. In the first experiment, their nitrogen balance was measured during the rehabilitation phase, and factors (type, severity of hemiparesis, activities of daily living, dysphagia and malnutrition status) related to it were evaluated. The second experiment was performed to describe the time course of nitrogen balance in 31 consecutive patients, with assessments made at admission and at discharge. Nitrogen balance was positive in all patients in the subacute phase. A significant difference was seen in nitrogen balance between high and low fat-free mass in male patients. In the chronic phase, nitrogen balance was positive in 96% of the patients. There was no significant difference in nitrogen balance between discharge and admission. In the subacute and chronic phases of stroke, it was confirmed that hypercatabolism had resolved and that intensive rehabilitation is possible in the convalescent period of stroke. © 2017 The British Dietetic Association Ltd.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

PubMed

Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

2017-04-03

BCR-ABL kinase domain (K D ) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-K D mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-K D . Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-K D mutation screening in late chronic phase CML patients for improved clinical management of disease.

Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

ClinicalTrials.gov

2015-10-29

B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic

PubMed Central

Wielders, Cornelia C. H.; van Loenhout, Joris A. F.; Morroy, Gabriëlla; Rietveld, Ariene; Notermans, Daan W.; Wever, Peter C.; Renders, Nicole H. M.; Leenders, Alexander C. A. P.; van der Hoek, Wim; Schneeberger, Peter M.

2015-01-01

Background Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007–2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever. Methods A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever. Results Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months. Conclusions A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever. PMID:26161658

Circulating endothelial cells are increased in chronic myeloid leukemia blast crisis.

PubMed

Godoy, C R T; Levy, D; Giampaoli, V; Chamone, D A F; Bydlowski, S P; Pereira, J

2015-06-01

We measured circulating endothelial precursor cells (EPCs), activated circulating endothelial cells (aCECs), and mature circulating endothelial cells (mCECs) using four-color multiparametric flow cytometry in the peripheral blood of 84 chronic myeloid leukemia (CML) patients and 65 healthy controls; and vascular endothelial growth factor (VEGF) by quantitative real-time PCR in 50 CML patients and 32 healthy controls. Because of an increase in mCECs, the median percentage of CECs in CML blast crisis (0.0146%) was significantly higher than in healthy subjects (0.0059%, P<0.01) and in the accelerated phase (0.0059%, P=0.01). There were no significant differences in the percentages of CECs in chronic- or active-phase patients and healthy subjects (P>0.05). In addition, VEGF gene expression was significantly higher in all phases of CML: 0.245 in blast crisis, 0.320 in the active phase, and 0.330 in chronic phase patients than it was in healthy subjects (0.145). In conclusion, CML in blast crisis had increased levels of CECs and VEGF gene expression, which may serve as markers of disease progression and may become targets for the management of CML.

Schema therapy for chronic depression: Results of a multiple single case series.

PubMed

Renner, Fritz; Arntz, Arnoud; Peeters, Frenk P M L; Lobbestael, Jill; Huibers, Marcus J H

2016-06-01

The aim of this study was to test the effects of individual schema therapy (ST) for patients with chronic depression. Using a multiple-baseline single case series design, patients with chronic major depressive disorder (N = 25) first entered a 6-24 weeks baseline phase; this phase functioned as a no-treatment control condition. Then, patients started a 12 week exploration phase during which symptoms and underlying schemas were explored; this phase functioned as an attention control condition. Next, patients received up to 65 sessions of individual ST. The Beck Depression Inventory II (BDI-II) and the Quick Inventory of Depressive Symptomatology (QIDS) were the primary outcome measures. The BDI-II was assessed once a week during all phases of the study resulting in 100 repeated assessments per participant on average. Mixed regression analysis was used to contrast change in symptoms during the intervention with change in symptoms during the baseline and exploration control phases. When compared to the no-treatment control period, the intervention had a significant, large effect on depressive symptoms (Cohen's d BDI-II = 1.30; Cohen's d QIDS = 1.22). Effects on secondary continuous outcomes were moderate to large. The small sample size and lack of a control group. These findings provide evidence that ST might be an effective treatment for patients with chronic depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study.

PubMed

Jain, Preetesh; Kantarjian, Hagop; Jabbour, Elias; Gonzalez, Graciela Nogueras; Borthakur, Gautam; Pemmaraju, Naveen; Daver, Naval; Gachimova, Evguenia; Ferrajoli, Alessandra; Kornblau, Steven; Ravandi, Farhad; O'Brien, Susan; Cortes, Jorge

2015-09-01

Ponatinib has shown efficacy in patients with refractory chronic myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed to investigate the activity and safety of ponatinib as first-line treatment for patients with chronic-phase CML. We did a single-arm, phase 2 trial at MD Anderson Cancer Center in Houston, TX, USA. Between May 3, 2012, and Sept 24, 2013, we enrolled patients with early (<6 months) chronic-phase CML and treated them with oral ponatinib once a day. Patients enrolled before July 25, 2013, were given a starting dose of 45 mg per day; we lowered this due to tolerability issues and patients enrolled after this date were given a starting dose of 30 mg per day. After a warning by the US Food and Drug Administration (FDA) in Oct 6, 2013, for vascular complications with ponatinib, we started all patients on aspirin 81 mg daily and reduced the dose of ponatinib to 30 mg or 15 mg per day for all patients. The primary endpoint was the proportion of patients who achieved complete cytogenetic response by 6 months in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01570868. We enrolled 51 patients. Median follow-up was 20·9 months (IQR 14·9–25·2). 43 patients were started on 45 mg ponatinib every day; eight patients were started on 30 mg per day. 43 (94%) of 46 evaluable patients achieved complete cytogenetic response at 6 months. Most frequent toxicities included skin-related effects (n=35; 69%) and elevated lipase (n=32; 63%). Cardiovascular events (mainly hypertension) occurred in 25 (49%) patients. Grade 3–4 myelosuppression occurred in 15 (29%) patients. Five (10%) patients developed cerebrovascular or vaso-occlusive disease. 43 (85%) patients needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated June 18, 2014, at the recommendation of the FDA due to concern about the increased risk of thromboembolism with ponatinib. Patients with newly diagnosed CML in chronic phase respond well to treatment with ponatinib, with most achieving a complete cytogenetic response. Dose adjustment, extensive monitoring, and counselling of the patients for thromboembolic events is needed for patients on ponatinib therapy. However, due to the risk of vascular thrombotic events and the availability of alternative options for these patients, other drugs should be considered first in the frontline setting. MD Anderson Cancer Center, National Cancer Institute, ARIAD Pharmaceutical.

Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant

ClinicalTrials.gov

2018-05-04

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Cytomegaloviral Infection; Hodgkin Lymphoma; Lymphadenopathy; Lymphoblastic Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine in Reducing CMV Related Complications in Patients With Blood Cancer Undergoing Donor Stem Cell Transplant

ClinicalTrials.gov

2018-02-16

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Bone Marrow Transplantation Recipient; Chronic Lymphocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic Cell Transplantation Recipient; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma

First-line treatment of chronic myeloid leukaemia.

PubMed

O'Dwyer, Michael

2010-02-01

Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase.

Genomic characterization of Imatinib resistance in CD34+ cell populations from chronic myeloid leukaemia patients.

PubMed

Joha, Sami; Dauphin, Véronique; Leprêtre, Frédéric; Corm, Sélim; Nicolini, Franck E; Roumier, Christophe; Nibourel, Olivier; Grardel, Nathalie; Maguer-Satta, Véronique; Idziorek, Thierry; Figeac, Martin; Laï, Jean-Luc; Quesnel, Bruno; Etienne, Gabriel; Guilhot, François; Lippert, Eric; Preudhomme, Claude; Roche-Lestienne, Catherine

2011-04-01

To ascertain genomic alterations associated with Imatinib resistance in chronic myeloid leukaemia, we performed high resolution genomic analysis of CD34(+) cells from 25 Imatinib (IM) resistant and 11 responders CML patients. Using patients' T-cells as reference, we found significant association between number of acquired cryptic copy number alterations (CNA) and disease phase (p=0.036) or loss of IM response for patients diagnosed in chronic phase (CP) (p=0.04). Recurrent cryptic losses were identified on chromosomes 7, 12 and 13. On chromosome 7, recurrent deletions of the IKZF1 locus were detected, for the first time, in 4 patients in CP. Copyright © 2010 Elsevier Ltd. All rights reserved.

A low bioimpedance phase angle predicts a higher mortality and lower nutritional status in chronic dialysis patients

NASA Astrophysics Data System (ADS)

Dumler Md, Francis

2010-04-01

Bioelectrical impedance analysis is an established technique for body composition analysis. The phase angle parameter, an index of body cell mass, tissue hydration, and membrane integrity, makes it suitable for assessing nutritional status and survivability. We evaluated the significance of a low phase angle value on nutritional status and mortality in 285 chronic dialysis patients during a longitudinal prospective observational study. Patients in the lower phase angle tertile had decreased body weight, body mass index, fat free mass, body cell mass, and lower serum albumin concentrations than those in the higher tertile (P<001). In addition, mortality rates were significantly lower (P=0.05) in the highest tertile patients. In conclusion, the phase angle is a useful method for identifying dialysis patients at high risk for malnutrition and increased mortality.

Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase

PubMed Central

Chuah, Charles T.; Nakamae, Hirohisa; Shen, Zhixiang X.; Bradley-Garelik, M. Brigid

2014-01-01

Asian patients with chronic myeloid leukemia (CML) tend to have different characteristics compared with patients from other regions, including younger age and smaller body size. The phase 3, open-label, randomized DASISION trial (NCT00481247), comparing dasatinib 100 mg once daily (QD) (n = 259) with imatinib 400 mg QD (n = 260) in newly diagnosed chronic phase CML (CML-CP), included a sizeable East Asian population (n = 60: dasatinib; n = 48: imatinib). In East Asian patients, dasatinib showed favorable 24-month rates of major molecular response (68% vs. 50% for imatinib) and complete cytogenetic response (92% vs. 88%), and more patients achieved BCR–ABL1 transcript levels ≤ 10% at 3 months with dasatinib (91% vs. 69%), similar to the overall population. Relative to non-East Asian patients, the incidence of rash, fluid-related events and grade 3/4 neutropenia and thrombocytopenia appeared to be higher in East Asians, regardless of treatment. Pharmacokinetic analysis revealed statistically non-significant increased dasatinib exposure among East Asian patients. Results support the use of dasatinib 100 mg QD as first-line CML treatment in both East Asian and non-East Asian patients. PMID:24289108

Individualized treatment with transcranial direct current stimulation in patients with chronic non-fluent aphasia due to stroke

PubMed Central

Shah-Basak, Priyanka P.; Norise, Catherine; Garcia, Gabriella; Torres, Jose; Faseyitan, Olufunsho; Hamilton, Roy H.

2015-01-01

While evidence suggests that transcranial direct current stimulation (tDCS) may facilitate language recovery in chronic post-stroke aphasia, individual variability in patient response to different patterns of stimulation remains largely unexplored. We sought to characterize this variability among chronic aphasic individuals, and to explore whether repeated stimulation with an individualized optimal montage could lead to persistent reduction of aphasia severity. In a two-phase study, we first stimulated patients with four active montages (left hemispheric anode or cathode; right hemispheric anode or cathode) and one sham montage (Phase 1). We examined changes in picture naming ability to address (1) variability in response to different montages among our patients, and (2) whether individual patients responded optimally to at least one montage. During Phase 2, subjects who responded in Phase 1 were randomized to receive either real-tDCS or to receive sham stimulation (10 days); patients who were randomized to receive sham stimulation first were then crossed over to receive real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per real-tDCS sessions and patients performed a picture naming task during stimulation. Patients' language ability was re-tested after 2-weeks and 2-months following real and sham tDCS in Phase 2. In Phase 1, despite considerable individual variability, the greatest average improvement was observed after left-cathodal stimulation. Seven out of 12 subjects responded optimally to at least one montage as demonstrated by transient improvement in picture-naming. In Phase 2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not sham. Despite individual variability with respect to optimal tDCS approach, certain montages result in consistent transient improvement in persons with chronic post-stroke aphasia. This preliminary study supports the notion that individualized tDCS treatment may enhance aphasia recovery in a persistent manner. PMID:25954178

First-line treatment of chronic myeloid leukaemia

PubMed Central

O'Dwyer, Michael

2010-01-01

Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase. PMID:23556068

A case of non-Hodgkin lymphoma in a patient with chronic myeloid leukemia.

PubMed

Găman, Amelia Maria; Dobrea, Camelia; Rotaru, Ionela

2013-01-01

Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), molecular analysis (Southern blot and RT-PCR) is necessary. Further studies are required to clarify the pathogenetic relationship between chronic myeloid leukemia and non-Hodgkin lymphomas.

Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

PubMed Central

Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

2014-01-01

Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia.

PubMed

Jabbour, Elias J; Hughes, Timothy P; Cortés, Jorge E; Kantarjian, Hagop M; Hochhaus, Andreas

2014-07-01

Despite vast improvements in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment.

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.

PubMed

Hochhaus, A; Saglio, G; Hughes, T P; Larson, R A; Kim, D-W; Issaragrisil, S; le Coutre, P D; Etienne, G; Dorlhiac-Llacer, P E; Clark, R E; Flinn, I W; Nakamae, H; Donohue, B; Deng, W; Dalal, D; Menssen, H D; Kantarjian, H M

2016-05-01

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

Nilotinib induced avascular necrosis of femoral head in an adult chronic myeloid leukemia patient.

PubMed

Thekkudan, Shinto Francis; Nityanand, Soniya

2018-06-01

We report a rare case of avascular necrosis of femoral head (AVNFH) in an adult chronic myeloid leukemia - chronic phase (CML-CP) patient during due course of therapy with second line Tyrosine Kinase Inhibitor (TKI), Nilotinib. A high index of clinical suspicion should be kept in any symptomatic CML patient on TKI's.

Granulocytic sarcoma in a patient with chronic myeloid leukaemia in complete haematological, cytogenetic and molecular remission.

PubMed

Kittai, Adam; Yu, Eun-Mi; Tabbara, Imad

2014-12-23

Granulocytic sarcoma, also known as myeloid sarcoma, is an extramedullary tumour composed of immature myeloid cells. Granulocytic sarcoma is typically found in patients with acute myeloid leukaemia, accelerated phase or blast crisis of chronic myeloid leukaemia, myelodysplastic syndrome, or as an isolated event without bone marrow involvement. We present a case of granulocytic sarcoma in a patient with chronic myeloid leukaemia in the setting of complete haematological, molecular and cytogenetic remission. Our patient was first treated with imatinib for chronic-phase chronic myeloid leukaemia. After maintaining remission for 42 months, he developed a granulocytic sarcoma in his spine. In this case report, we describe our case, along with the three other cases reported in the literature. In addition to being a rare diagnosis, this case demonstrates the importance of being vigilant in diagnosing the cause of back pain and atypical symptoms in patients with a history of leukaemia. 2014 BMJ Publishing Group Ltd.

Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging.

PubMed

Yamada, Kiyoyasu; Isobe, Satoshi; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Ohshima, Satoru; Hirai, Makoto; Sawada, Ken; Murohara, Toyoaki

2012-04-01

To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. MR can differentiate reversible from irreversible myocardial damage after myocardial infarction. MR is a useful modality to noninvasively differentiate the infarct stages. The O/I is an important index to decide therapeutic strategies.

Dasatinib-induced pulmonary arterial hypertension - A rare late complication.

PubMed

Ibrahim, Uroosa; Saqib, Amina; Dhar, Vidhya; Odaimi, Marcel

2018-01-01

Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

ClinicalTrials.gov

2013-01-22

Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study.

PubMed

Mahon, François-Xavier; Boquimpani, Carla; Kim, Dong-Wook; Benyamini, Noam; Clementino, Nelma Cristina D; Shuvaev, Vasily; Ailawadhi, Sikander; Lipton, Jeffrey Howard; Turkina, Anna G; De Paz, Raquel; Moiraghi, Beatriz; Nicolini, Franck E; Dengler, Jolanta; Sacha, Tomasz; Takahashi, Naoto; Fellague-Chebra, Rafik; Acharya, Sandip; Wong, Stephane; Jin, Yu; Hughes, Timothy P

2018-04-03

Treatment-free remission (TFR)-that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response-is an emerging treatment goal in chronic myeloid leukemia (CML). To evaluate TFR after discontinuation of second-line nilotinib therapy. Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905). 63 centers in 18 countries. Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib. Novartis Pharmaceuticals Corporation.

Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Agodoa, Lawrence Y.; Astor, Brad C.; Bakris, George L.; Cleveland, William H.; Charleston, Jeanne; Contreras, Gabriel; Faulkner, Marquetta L.; Gabbai, Francis B.; Gassman, Jennifer J.; Hebert, Lee A.; Jamerson, Kenneth A.; Kopple, Joel D.; Kusek, John W.; Lash, James P.; Lea, Janice P.; Lewis, Julia B.; Lipkowitz, Michael S.; Massry, Shaul G.; Miller, Edgar R.; Norris, Keith; Phillips, Robert A.; Pogue, Velvie A.; Randall, Otelio S.; Rostand, Stephen G.; Smogorzewski, Miroslaw J.; Toto, Robert D.; Wang, Xuelei

2013-01-01

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) PMID:20818902

Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer

ClinicalTrials.gov

2013-01-08

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Relapsing Chronic Myelogenous Leukemia; Thrombocytopenia; Untreated Adult Acute Myeloid Leukemia

Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant

ClinicalTrials.gov

2017-09-01

Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Juvenile Myelomonocytic Leukemia; Previously Treated Childhood Rhabdomyosarcoma; Previously Treated Myelodysplastic Syndromes; Pulmonary Complications; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

PubMed

Rosshandler, Yasmin; Shen, Ann Q; Cortes, Jorge; Khoury, Hanna Jean

2016-05-01

Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.

Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

PubMed

Jovanovska, Anamarija; Stoilovska, Bojana; Mileva, Magdalena; Miladinova, Daniela; Majstorov, Venjamin; Ugrinska, Ana

2018-05-20

Thyroid uptake of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) during parathyroid scintigraphy can be affected by various conditions. To evaluate the frequency of absent 99m Tc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. The early planar images of dual phase Tc 99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. Absent 99m Tc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99m Tc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

Comparison of Direct Oral Anticoagulants and Warfarin in the Treatment of Deep Venous Thrombosis in the Chronic Phase.

PubMed

Wakakura, Shingo; Hara, Fumihiko; Fujino, Tadashi; Hamai, Asami; Ohara, Hiroshi; Kabuki, Takayuki; Harada, Masahiko; Ikeda, Takanori

2018-01-27

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

ClinicalTrials.gov

2017-12-15

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Hodgkin Lymphoma; Adult Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Cytomegaloviral Infection; Hematopoietic and Lymphoid Cell Neoplasm; HLA-A*0201 Positive Cells Present; Myelodysplastic Syndrome; Adult Lymphoblastic Lymphoma; Chronic Lymphocytic Leukemia; Myelofibrosis; Myeloproliferative Neoplasm

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PubMed

Voskrebenzev, Andreas; Gutberlet, Marcel; Klimeš, Filip; Kaireit, Till F; Schönfeld, Christian; Rotärmel, Alexander; Wacker, Frank; Vogel-Claussen, Jens

2018-04-01

In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Combination of low-dose imatinib plus nilotinib for the treatment of chronic-phase chronic myeloid leukaemia after imatinib failure.

PubMed

Gómez-Almaguer, David; Saldaña-Vázquez, Roxana; Tarín-Arzaga, Luz; Herrera-Rojas, Miguel Angel; Vázquez-Mellado de Larracoechea, Alberto; Cantú-Rodríguez, Olga Graciela; Gutiérrez-Aguirre, Cesar Homero; Jaime-Pérez, José Carlos

2016-08-01

This is a feasibility study to evaluate whether simultaneous administration of low doses of imatinib and nilotinib in chronic-phase chronic myeloid leukaemia (CP-CML) patients has the potential for transcript elimination after failure to imatinib. Ten patients were enrolled; eight had cytogenetic relapse and two had confirmed loss of major molecular response (MMR). At baseline, BCR-ABL kinase domain mutation was detected in four patients. After 6 months of therapy, major cytogenetic response, complete cytogenetic response, and MMR were achieved in seven, four, and four patients, respectively. Grade 4 thrombocytopenia developed in one patient, and grade 1 skin rash in four. These results suggest that imatinib might have inhibitory effects on the clearance of nilotinib, increasing its efficacy. This dual therapy was well tolerated and resulted in improvement of cytogenetic and molecular responses in patients with CP-CML after failure to imatinib. ClinicalTrials.gov registration number: NCT01819389.

MR-1 blocks the megakaryocytic differentiation and transition of CML from chronic phase to blast crisis through MEK dephosphorylation

PubMed Central

Zhao, W; He, H; Ren, K; Li, B; Zhang, H; Lin, Y; Shao, R-g

2013-01-01

Chronic myelogenous leukemia (CML) evolves from a chronic phase characterized by the Philadelphia chromosome as the sole genetic abnormality and the accumulation of mature cells in peripheral blood into blast crisis, which is characterized by the rapid expansion of myeloid- or lymphoid-differentiation-arrested blast cells. Although ample studies have been conducted on the disease progress mechanisms, the underlying molecular mechanisms of the malignant phenotype transition are still unclear. In this study, we have shown that myofibrillogenesis regulator-1 (MR-1) was overexpressed in blast crisis patients and leukemic cells, but there was little trace expressed in healthy individuals and in most patients in CML chronic phase. MR-1 could inhibit the differentiation of myeloid cells into megakaryocytic lineages and accelerate cell proliferation. The molecular mechanism responsible for these effects was the interaction of MR-1 with MEK, which blocked the MEK/ERK signaling pathway by dephosphorylating MEK. Our results provide compelling and important evidence that MR-1 might act as a diagnostic marker and potential target of CML progression from chronic phase to blast crisis. PMID:23542180

Impact of Imatinib on the Fertility of Male Patients with Chronic Myelogenous Leukaemia in the Chronic Phase.

PubMed

Chang, Xiaohui; Zhou, Lin; Chen, Xiaoxia; Xu, Baoli; Cheng, Yubin; Sun, Shujun; Fang, Meiyun; Xiang, Yang

2017-12-01

Imatinib is a first-line tyrosine kinase inhibitor for treating chronic myelogenous leukaemia (CML) and has greatly improved the prognosis of this disease. An increasing number of CML patients of reproductive age are diagnosed each year, and the impact of imatinib on fertility is a major concern. Providing useful advice to these patients regarding the choice of their therapeutic treatment is very important. This study examined the impact of imatinib on the fertility of male patients with CML in the chronic phase. We performed a study of 48 adult male CML patients in the chronic phase (CML-CP), 50 healthy control subjects, and 10 male patients with infertility. Imatinib levels in semen and plasma were measured using high-performance liquid chromatography/mass spectrometry. We examined the effects of imatinib on sperm parameters and the male reproductive system using a computer-assisted sperm assay and ultrasound, respectively. We analysed sex hormone levels in the sera of CML-CP patients using an enzyme-linked immunosorbent assay. Imatinib levels in semen were comparable to plasma levels in CML-CP patients. CML-CP patients treated with imatinib exhibited reduced sperm density, counts, survival rates, and activity. Ultrasound demonstrated that the shape and size of the testis and epididymis in CML-CP patients undergoing imatinib treatment were normal. However, 19 of these patients exhibited a hydrocele in their tunica vaginalis, with a large dark area of effusion (0.7-2.9 cm in width). Sex hormone levels in the sera of the CML-CP patients were normal. These results suggest that imatinib crosses the blood-testis barrier and reduces sperm density, sperm count, survival rates, and activity in CML-CP patients. However, imatinib did not affect the structure of reproductive organs or sex hormone levels.

Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia.

PubMed

Ruggiu, Mathilde; Oberkampf, Florence; Ghez, David; Cony-Makhoul, Pascale; Beckeriche, Florence; Cano, Isabelle; Taksin, Anne L; Benbrahim, Omar; Ghez, Stéphanie; Farhat, Hassan; Rigaudeau, Sophie; de Gunzburg, Noémie; Lara, Diane; Terre, Christine; Raggueneau, Victoria; Garcia, Isabel; Spentchian, Marc; De Botton, Stéphane; Rousselot, Philippe

2017-11-28

Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic response (HR) rate was 81.3%. Median overall survival (OS), event free survival and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively. All except one patient were treated as out-patients after the first cycle. Five patients were bridged to allogenic hematopoietic stem cells transplant. The combination of a TKI and azacytidine is a safe and efficient regiment for patients with CML patients in advanced phases.

A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia.

PubMed

Tomiyama, Y; Miyakawa, Y; Okamoto, S; Katsutani, S; Kimura, A; Okoshi, Y; Ninomiya, H; Kosugi, H; Nomura, S; Ozaki, K; Ikeda, Y; Hattori, T; Katsura, K; Kanakura, Y

2012-05-01

Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has shown efficacy and safety in chronic immune thrombocytopenia (ITP). However, ethnic differences in eltrombopag exposure have been reported: area under the curve exposure to eltrombopag was 87% greater among ITP patients of East Asian descent than among ITP patients of non-East Asian ITP descent. To evaluate the efficacy and safety of eltrombopag by using, in Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved in the USA and Europe. We examined 23 Japanese patients with previously treated chronic ITP with a platelet count of < 30,000 μL(-1) in a multicenter study comprising a randomized, double-blind, placebo-controlled phase for 6-week evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6-month evaluation (23 eltrombopag). The response rate (platelet count of ≥ 50,000 μL(-1) ) at week 6 of the 6-week double-blind phase was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten of 23 patients (43.5%) responded for ≥ 75% of predefined assessment visits during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to 12.5 mg of eltrombopag, which was administered within the first 3 weeks of eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared with baseline. Eltrombopag was generally well tolerated; one patient experienced a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for the management of Japanese patients with chronic ITP (NCT00540423). © 2012 International Society on Thrombosis and Haemostasis.

Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

ClinicalTrials.gov

2016-02-20

Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

Case of relentless chronic phase of chronic myeloid leukaemia.

PubMed

Chan, Onyee; Chen, Hao; Krishnadasan, Ravitharan; Anwer, Faiz

2016-06-22

Initial treatment of chronic phase chronic myeloid leukaemia is straightforward in today's era of tyrosine kinase inhibitors. However, managing refractory cases remain a major challenge due to the multiple factors that can influence decision-making, including medication tolerance, disease burden, mutation status, comorbidities, availability of donor, and fitness for an ablative conditioning. We report a male patient presenting with chronic phase chronic myeloid leukaemia who was treated with 5 different tyrosine kinase inhibitors either due to intolerance and/or failed response. He subsequently received 2 haploidentical haematopoietic stem cells transplants before achieving complete remission. This case highlights various treatment options, need for vigilant disease monitoring, and the possibility of complete positive response even after many lines of therapy failure. 2016 BMJ Publishing Group Ltd.

Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors.

PubMed

Sasaki, Koji; Kantarjian, Hagop M; Jain, Preetesh; Jabbour, Elias J; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Takahashi, Koichi; Pemmaraju, Naveen; Daver, Naval; Pierce, Sherry A; O'Brien, Susan M; Cortes, Jorge E

2016-01-15

Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment. Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction. A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period. In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. © 2015 American Cancer Society.

Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases.

PubMed

Gofshteyn, Jacqueline S; Wilfong, Angus; Devinsky, Orrin; Bluvstein, Judith; Charuta, Joshi; Ciliberto, Michael A; Laux, Linda; Marsh, Eric D

2017-01-01

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT

ClinicalTrials.gov

2018-04-04

Adult Hodgkin Lymphoma; Adult Myelodysplastic Syndrome; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Hodgkin Lymphoma; Childhood Myelodysplastic Syndrome; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Myelofibrosis; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Non-Hodgkin Lymphoma

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

PubMed

Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

2016-01-01

The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

Evaluating the impact of a switch to nilotinib on imatinib-related chronic low-grade adverse events in patients with CML-CP: the ENRICH study

PubMed Central

Cortes, Jorge E.; Lipton, Jeffrey H.; Miller, Carole B.; Busque, Lambert; Akard, Luke P.; Pinilla-Ibarz, Javier; Keir, Christopher; Warsi, Ghulam; Lin, Felice P.; Mauro, Michael J.

2016-01-01

Background Many patients with chronic myeloid leukemia in chronic phase (CML-CP) experience chronic treatment-related adverse events (AEs) on imatinib therapy. These AEs can impair quality of life (QOL) and lead to reduced treatment adherence, which is associated with poor clinical outcomes. Patients and Methods In the phase 2 Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events (ENRICH) study (N = 52), the impact of switching patients with imatinib-related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated. Results Three months after switching to nilotinib, 84.6% of patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% resolved within 3 months of switching to nilotinib. Among evaluable patients, most had improvements in overall QOL after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of MMR was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported on nilotinib were typically grade 1/2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib due to new or worsening AEs. Conclusions Overall, results from ENRICH demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with CML-CP in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018. PMID:26993758

Treatment of chronic myelogenous leukemia with interleukin-2: a phase II study in 21 patients.

PubMed

Vey, N; Blaise, D; Lafage, M; Olive, D; Viens, P; Baume, D; Camerlo, J; Stoppa, A M; Gabus, R; Brandely, M; Hercend, T; Maraninchi, D

1999-03-01

We designed a phase II study to assess the activity of recombinant interleukin-2 (rIL-2) in patients with chronic myelogenous leukemia (CML). Study population included 11 patients in the chronic phase of CML (6 in hematologic remission and 5 with active disease), 6 patients in the accelerated phase, and 4 in blastic phase of CML. Patients received three 5-day cycles administrated every other week. rIL-2 was given as intravenous bolus infusions of 8 x 10(6) IU/m2 three times a day during cycle 1 and twice a day during cycles 2 and 3. Response to rIL-2 was assessed on day 45. No hematologic response was achieved in the patients with evaluable disease. One patient in hematologic remission with rIL-2 achieved a major response (from 72% to 9% Ph+ metaphases), and two patients had some degree of reduction of Ph+ metaphases. Responses were short-lived (< 6 months), but two of these three patients achieved a new cytogenetic response with interferon given post-rIL-2. A significant immune activation was achieved with rIL-2 including a marked increase in CD3+/CD25+ cells, CD56+ cells, and in natural killer/lymphokine activated killer cell cytotoxic activity. These results confirm preclinical studies, which showed that IL-2 has antileukemic activity in CML. However, the responses observed were short lived and restricted to a subgroup of patients with low disease burden. This invites further studies testing its impact in situations of minimal disease or in combination with other cytokines.

Chronic health needs immediately after natural disasters in middle-income countries: the case of the 2008 Sichuan, China earthquake.

PubMed

Chan, Emily Y Y; Kim, Jackie

2011-04-01

Few studies have focused on chronic health needs immediately after natural disasters in middle-income countries. This study examines chronic medical needs during the acute phase after the 2008 Sichuan earthquake. A descriptive, cross-sectional study was conducted in an emergency triage clinic in Sichuan, China. Information on physical, social, and public health preparedness was collected in predesigned templates. Descriptive and Pearson's χ association analyses were conducted. One hundred and eighty-two evacuees were received at the triage site. Of these, 54% required trauma treatment and 77% of evacuated patients who required care had underlying chronic medical conditions. Tetanus immunizations and the possession of chronic health medication were low, particularly among older patients. Chronic health needs constituted a significant proportion of emergency care during the acute phase in the study population. Effective post-disaster assistance requires attention to demographic and epidemiological population profiles.

Impaired theta phase-resetting underlying auditory N1 suppression in chronic alcoholism.

PubMed

Fuentemilla, Lluis; Marco-Pallarés, Josep; Gual, Antoni; Escera, Carles; Polo, Maria Dolores; Grau, Carles

2009-02-18

It has been suggested that chronic alcoholism may lead to altered neural mechanisms related to inhibitory processes. Here, we studied auditory N1 suppression phenomena (i.e. amplitude reduction with repetitive stimuli) in chronic alcoholic patients as an early-stage information-processing brain function involving inhibition by the analysis of the N1 event-related potential and time-frequency computation (spectral power and phase-resetting). Our results showed enhanced neural theta oscillatory phase-resetting underlying N1 generation in suppressed N1 event-related potential. The present findings suggest that chronic alcoholism alters neural oscillatory synchrony dynamics at very early stages of information processing.

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity

PubMed Central

Cao, Dianjun; Cao, Qian M.; Subramaniam, Sakthivel; Yugo, Danielle M.; Heffron, C. Lynn; Rogers, Adam J.; Kenney, Scott P.; Tian, Debin; Matzinger, Shannon R.; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-01-01

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ–specific CD4+ T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α–specific CD8+ T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E. PMID:28630341

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

PubMed

Cao, Dianjun; Cao, Qian M; Subramaniam, Sakthivel; Yugo, Danielle M; Heffron, C Lynn; Rogers, Adam J; Kenney, Scott P; Tian, Debin; Matzinger, Shannon R; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-07-03

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4 + T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8 + T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2018-05-24

Acute Myeloid Leukemia; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

The efficacy of negative pressure wound therapy in treating sacroiliac joint tuberculosis with a chronic sinus tract: a case series.

PubMed

Luo, Xiaobo; Tang, Xiangyu; Ma, Yuanzheng; Zhang, Yonggang; Fang, Shuzhi

2015-08-06

Tuberculous sacroiliitis with abscess accounts for approximately 50 % of all sacroiliac joint tuberculosis cases. Tuberculous abscesses spread into the sacroiliac joint capsule, subcutaneous tissue, and the skin, and finally becomes a skin sinus. As there are no previous reports about sacroiliac joint tuberculosis with a chronic sinus, we evaluated its clinical characteristics and management by negative pressure wound therapy. A retrospective analysis of 12 patients with sacroiliac joint tuberculosis with chronic sinuses treated between January 2005 and January 2010 was conducted. Patients were treated with negative pressure wound therapy (NPWT). Treatment was divided into three phases: control phase, standard dressing changes daily for 4 weeks; interphase washout period, dressing changes every 3 days for 1 week; and intervention phase, no dressing changes until minimal sinus tract drainage (<5 ml per 24 h). Outcomes including the sinus healing time and the drainage volume were evaluated. The mean follow-up was 37.1 months. Sinus healing was observed at an average of 25.25 ± 7.23 (range, 20-42) days after initial treatment. The mean volume of drainage did not change during the control phase, but decreased from 29.17 ± 16.63 to 0.25 ± 0.87 ml in the intervention phase. The mean daily reduction of wound volume, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in the intervention phase was greater than in the control phase (P < 0.05). Anti-tubercular therapy was administered an average of 14.00 ± 2.95 (range, 12-18) months. ESR and CRP returned to normal within 3 months after the sinus closure. Bony fusion was observed in 5 (41.7 %) patients, and fibrous ankylosis in the other patients at last follow-up. All patients healed uneventfully. Early diagnosis of sacroiliac joint tuberculosis with a chronic sinus can be difficult. NPWT provides better healing of sacroiliac joint tuberculosis with a chronic sinus than standard dressing changes.

Effects of sensorimotor foot training on the symmetry of weight distribution on the lower extremities of patients in the chronic phase after stroke

PubMed Central

Goliwas, Magdalena; Kocur, Piotr; Furmaniuk, Lech; Majchrzycki, Marian; Wiernicka, Marzena; Lewandowski, Jacek

2015-01-01

[Purpose] To assess the effects of sensorimotor foot stimulation on the symmetry of weight distribution on the feet of patients in the chronic post-stroke phase. [Subjects and Methods] This study was a prospective, single blind, randomized controlled trial. In the study we examined patients with chronic stroke (post-stroke duration > 1 year). They were randomly allocated to the study group (n=8) or to the control group (n=12). Both groups completed a standard six-week rehabilitation programme. In the study group, the standard rehabilitation programme was supplemented with sensorimotor foot stimulation training. Each patient underwent two assessments of symmetry of weight distribution on the lower extremities with and without visual control, on a treadmill, with stabilometry measurements, and under static conditions. [Results] Only the study group demonstrated a significant increase in the weight placed on the leg directly affected by stroke, and a reduction in asymmetry of weight-bearing on the lower extremities. [Conclusion] Sensorimotor stimulation of the feet enhanced of weight bearing on the foot on the side of the body directly affected by stroke, and a decreased asymmetry of weight distribution on the lower extremities of patients in the chronic post-stroke phase. PMID:26504326

Effects of sensorimotor foot training on the symmetry of weight distribution on the lower extremities of patients in the chronic phase after stroke.

PubMed

Goliwas, Magdalena; Kocur, Piotr; Furmaniuk, Lech; Majchrzycki, Marian; Wiernicka, Marzena; Lewandowski, Jacek

2015-09-01

[Purpose] To assess the effects of sensorimotor foot stimulation on the symmetry of weight distribution on the feet of patients in the chronic post-stroke phase. [Subjects and Methods] This study was a prospective, single blind, randomized controlled trial. In the study we examined patients with chronic stroke (post-stroke duration > 1 year). They were randomly allocated to the study group (n=8) or to the control group (n=12). Both groups completed a standard six-week rehabilitation programme. In the study group, the standard rehabilitation programme was supplemented with sensorimotor foot stimulation training. Each patient underwent two assessments of symmetry of weight distribution on the lower extremities with and without visual control, on a treadmill, with stabilometry measurements, and under static conditions. [Results] Only the study group demonstrated a significant increase in the weight placed on the leg directly affected by stroke, and a reduction in asymmetry of weight-bearing on the lower extremities. [Conclusion] Sensorimotor stimulation of the feet enhanced of weight bearing on the foot on the side of the body directly affected by stroke, and a decreased asymmetry of weight distribution on the lower extremities of patients in the chronic post-stroke phase.

Chronic hepatitis B virus infection in Asian countries.

PubMed

Merican, I; Guan, R; Amarapuka, D; Alexander, M J; Chutaputti, A; Chien, R N; Hasnian, S S; Leung, N; Lesmana, L; Phiet, P H; Sjalfoellah Noer, H M; Sollano, J; Sun, H S; Xu, D Z

2000-12-01

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.

Management of Advanced-Phase Chronic Myelogenous Leukemia.

PubMed

Radich, Jerald P

2016-05-01

Chronic myelogenous leukemia represents the poster child of successful precision medicine in cancer, with amazing survival results achieved with targeted tyrosine kinase inhibitors (TKIs) in many patients with chronic-phase disease. Unfortunately, however, this good news has not extended to patients in blast crisis, for whom survival has not clearly been improved with TKIs. During his presentation at the NCCN 21st Annual Conference, Jerald P. Radich, MD, briefly explored the biology behind advanced-stage disease and several of the molecular findings in disease progression. He also reviewed some of the therapeutic options in advanced disease, emphasizing that transplantation, although fraught with some difficulties, offers the best long-term prognosis for patients in blast crisis. Copyright © 2016 by the National Comprehensive Cancer Network.

COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy.

PubMed

Vondrichova, Tereza; de Capretz, Annika; Parikh, Hemang; Frenander, Christofer; Asman, Peter; Aberg, Magnus; Groop, Leif; Hallengren, Bengt; Lantz, Mikael

2007-06-01

Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy. The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy. Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes. Clinic of Endocrinology, University Hospital, Malmö, Sweden. Patients in acute severe or in chronic phase of ophthalmopathy. Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes. A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%. We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.

Substitution scenario in follow-up of chronic cancer patients in primary care: prevalence, disease duration and estimated extra consultation time.

PubMed

van Dipten, C; Olde Hartman, T C; Biermans, M C J; Assendelft, W J J

2016-02-01

The incidence of cancer as well as survival rates for it are increasing. It is debated whether care in the chronic phase of cancer can be positioned in primary care due to doubts about capacity and workload. To estimate GPs' extra consultation time if they assume responsibility for the care in the chronic phase of cancer. Retrospective cohort study. Estimation of extra consultation time by quantifying prevalence, incidence, survival, number of chronic cancer patients, current practice contacts and registration of risk factors in patients with all types of cancers. The most prevalent types of cancer (with 5-year survival rates) are as follows: breast cancer (91.5%), colorectal cancer (63.8%), prostate cancer (78.3%), melanoma (91.9%) and bladder and urinary tract cancer (77.3%). Primary care practices include ~32 chronic cancer patients, with a potential extra consultation time of ~19 hours per year per 1000 patients. One-third (35%) are already in a chronic disease management programme and 57% were diagnosed >5 years ago. Registration of risk factors for cancer is incomplete, but of better quality when comorbidity is present. Numbers of chronic cancer patients and possible time investment by primary care professionals in the case of a substitution scenario should not be a limiting factor for transition of follow-up from secondary to primary care, as most of the patients were diagnosed >5 years ago and a large proportion of these patients are already monitored in an existing chronic care programme. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sunitinib in Treating Patients With Idiopathic Myelofibrosis

ClinicalTrials.gov

2014-05-12

Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Hairy Cell Leukemia

Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial.

PubMed

Gore, Lia; Kearns, Pamela R; de Martino, Maria Lucia; Lee; De Souza, Carmino Antonio; Bertrand, Yves; Hijiya, Nobuko; Stork, Linda C; Chung, Nack-Gyun; Cardos, Rocio Cardenas; Saikia, Tapan; Fagioli, Franca; Seo, Jong Jin; Landman-Parker, Judith; Lancaster, Donna; Place, Andrew E; Rabin, Karen R; Sacchi, Mariana; Swanink, Rene; Zwaan, C Michel

2018-05-01

Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome-positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients < 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response > 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) > 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response > 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR > 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.

Treatment patterns and prognostic indicators of response to therapy among patients with chronic myeloid leukemia in Australia, Canada, and South Korea.

PubMed

Whiteley, Jennifer; Iyer, Shrividya; Candrilli, Sean D; Kaye, James A

2015-02-01

Given the multiple options for treatment of chronic-phase chronic myeloid leukemia (CML) with tyrosine kinase inhibitors, our objective was to understand treatment patterns in routine practice and prognostic indicators of response. We conducted a retrospective medical record review of 681 patients with CML in Australia, Canada, and South Korea. Eligible patients had a diagnosis of chronic-phase CML, were Philadelphia chromosome and/or BCR-ABL positive, were aged 18 years or older, and had been treated with first-line imatinib therapy between January 2005 and September 2010. Data on patient demographics, medical history (e.g., comorbidities, Sokal score), and treatment characteristics (e.g., time to initiation, therapy duration) were abstracted. Descriptive analyses were stratified by country and therapy line. Prognostic indicators of response to imatinib were evaluated using multivariable logistic regression, adjusting for country, patient demographics, medical history, treatment characteristics, and side effects. Hematologic, cytogenetic, and molecular responses at 3, 6, 12, and 18 months following initiation of each therapy line. Patients' average age was 57 years, and 59% were male. Overall, imatinib was initiated approximately 4 months following CML diagnosis. Complete or major molecular response (C/MMR) at 6 months following imatinib initiation was 54% in Australia, 22% in Canada, and 38% in South Korea. At 18 months, over 60% of patients achieved C/MMR. Approximately 30% of patients discontinued imatinib primarily due to intolerance and lack of response. Among patients who received second-line treatment, dasatinib was used more frequently than nilotinib. Multivariable regression results indicated Sokal score was identified as a prognostic indicator of response to imatinib therapy at several time points. There are several limitations to this study. First, we selected a convenience sample of patients and physicians and therefore results may not be representative of the true population of patients with chronic-phase CML. Second, data were entered by the selected physician and could be subject to data entry errors or inaccuracies. Third, limited information was collected from the patient records, and it is possible that we did not capture additional prognostic or confounding factors related to the measured outcomes. Next, because this was an analysis of previously documented data (i.e., retrospective), we were unable to provide a priori definitions of response. Finally, multivariable analyses were limited to imatinib-related outcomes. Treatment patterns and prognostic indicators differed by country. Health care providers, payers, and patients can utilize these results to inform treatment and policies aimed at improving the effectiveness of care for patients with chronic-phase CML.

Changes in spatiotemporal gait parameters following intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy.

PubMed

Vo, Mary L; Chin, Russell L; Miranda, Caroline; Latov, Norman

2017-10-01

Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures. We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors. Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength. Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. © 2017 Wiley Periodicals, Inc.

Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors.

PubMed

Weir, Matthew R; Bushinsky, David A; Benton, Wade W; Woods, Steven D; Mayo, Martha R; Arthur, Susan P; Pitt, Bertram; Bakris, George L

2018-05-01

Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

IMATINIB 800MG DAILY INDUCES DEEPER MOLECULAR RESPONSES THAN IMATINIB 400MG DAILY: RESULTS OF SWOG S0325, AN INTERGROUP RANDOMIZED PHASE II TRIAL IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA

PubMed Central

Deininger, Michael W.; Kopecky, Kenneth J.; Radich, Jerald P.; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D.; Tallman, Martin; Wadleigh, Martha; Larson, Richard A.; Lipton, Jeffrey H.; Slovak, Marilyn L.; Appelbaum, Frederick R.; Druker, Brian J.

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukemia (CP-CML) is 400mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematologic and cytogenetic response to IM400 vs. imatinib 400mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P=0.038; 3-log reduction: 53% vs. 35%, P=0.049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2.9-fold lower than in the IM400 arm (P=0.010). Complete haematologic response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P=0.040). Grade 3–4 toxicities were more common for IM800 (58% vs. 31%, P=0.0007), and were most commonly haematologic. Few patients have relapsed, progressed or died, but progression-free (P=0.048) and relapse-free (P=0.031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper molecular responses than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. PMID:24383843

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

PubMed

Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C

PubMed Central

Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients. PMID:28614389

Association of phase angle on bioelectrical impedance analysis and dialysis frequency with survival of chronic hemodialysis patients

NASA Astrophysics Data System (ADS)

Muzasti, R. A.; Lubis, H. R.

2018-03-01

Phase angle, a parameter by Bioelectrical Impedance Analysis, can detect body composition changes, so it can be used as a prognostic indicator in some chronic conditions. This study was for determining the relationship between PhA and hemodiálisis frequency with the survival of chronic hemodiálisis patients. This longitudinal retrospective study involved 173 chronic hemodiálisis patients at Rasyida Renal Hospital. The Kaplan-Meier method is used to determine the survival. Cox proportional hazard analysis is used to determine which variables significantly increase mortality. During the study period, 89 patients underwent hemodiálysis 3x a week (4 hours/session), and 84 patients underwent HD 2x a week (5 hours/session). Demographic and clinical characteristics in both groups were similar. There was no difference in PhA value in groups of 3x a week and group 2x a week (4.02 ± 1.13 vs 4.25 ± 1.12). Patients with twice a week hemodiálisis had a shorter survival than the 3x week group (35.14 ± 2.76 vs 38.62 ± 3.03) although it was not statistically significant (p = 0.126).

Inner neural retina loss in central retinal artery occlusion.

PubMed

Ikeda, Fumiko; Kishi, Shoji

2010-09-01

To report morphologic retinal changes and visual outcomes in acute and chronic central retinal artery occlusion (CRAO). We reviewed ten eyes of ten patients with CRAO (age, 65.3 ± 10.2 years) and measured retinal thicknesses at the central fovea and the perifovea using optical coherence tomography (OCT) over 8 ± 4 months. During the acute phase (within 10 days), the mean inner retinal thicknesses were 148% and 139% of normal values at 1 mm nasal and temporal to the fovea. They decreased to 22% and 11% of normal inner retinal thickness during the chronic phase (3 months or later). The retinal thickness at the perifovea decreased linearly until 3 months but was stable during the chronic phase. In contrast, the foveal thickness increased slightly in the acute phase but was equivalent to the normal level during the chronic phase. As a result of inner retinal atrophy, the foveal pit was shallow during the chronic phase. The final visual acuity was correlated positively with retinal thickness at the perifovea during the chronic CRAO phase. OCT showed that inner retinal necrosis with early swelling and late atrophy occurred in CRAO. The fovea and outer retina appeared to be excluded from ischemic change. The residual inner retina at the perifovea determined the final visual outcomes.

Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study.

PubMed

Martinelli, Giovanni; Oehler, Vivian G; Papayannidis, Cristina; Courtney, Rachel; Shaik, M Naveed; Zhang, Xiaoxi; O'Connell, Ashleigh; McLachlan, Karen R; Zheng, Xianxian; Radich, Jerald; Baccarani, Michele; Kantarjian, Hagop M; Levin, Wendy J; Cortes, Jorge E; Jamieson, Catriona

2015-08-01

Activation of the Hedgehog signalling pathway contributes to cancer progression and the development of myeloid leukaemia stem cell therapeutic resistance. We aimed to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose of the selective Hedgehog antagonist PF-04449913 in myeloid malignancies. We undertook an open-label, dose-finding, standard 3+3 design phase 1 study of PF-04449913 in adult patients with acute myeloid leukaemia, chronic myeloid leukaemia, chronic myelomonocytic leukaemia, myelodysplastic syndrome, or myelofibrosis who were refractory, resistant, or intolerant to previous treatments, at three centres in the USA and one in Italy. Patients who had newly diagnosed, untreated disease were included if they were not eligible for standard treatment options or if standard treatments were not deemed appropriate. Patients received PF-04449913 once daily continuously until disease progression, unacceptable toxic effects, or patient withdrawal for up to 12 28-day cycles. Additional cycles were given if patients showed evidence of clinical benefit. The starting dose was 5 mg and was increased by 100% until the first dose-limiting toxic effect (DLT) and by 50% thereafter, in keeping with a 3+3 clinical trial statistical design. The primary endpoint was first-cycle DLTs. Secondary endpoints were safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity. This trial is registered with ClinicalTrials.gov, number NCT00953758. Between March 24, 2010, and Sept 7, 2012, 47 patients were enrolled and included in the study: 28 with acute myeloid leukaemia, six with myelodysplastic syndrome, five with chronic myeloid leukaemia (two with chronic-phase and three with blast-phase disease), one with chronic myelomonocytic leukaemia, and seven with myelofibrosis. Patients received PF-04449913 once daily at 5 mg (n=3), 10 mg (n=3), 20 mg (n=4), 40 mg (n=4), 80 mg (n=8), 120 mg (n=3), 180 mg (n=3), 270 mg (n=5), 400 mg (n=9), and 600 mg (n=5). Two patients experienced DLTs (one each in the 80 mg and 600 mg dose groups). The MTD for PF-04449913 was established to be 400 mg once daily. Of the 47 patients enrolled, 28 (60%) experienced treatment-related adverse events, three of which were grade 4 in severity. The most common treatment-related adverse events included dysgeusia (13 [28%] patients), decreased appetite (nine [19%]), and alopecia (seven [15%]). None of the 15 deaths reported were treatment related. Pharmacokinetics seemed to be dose proportional. The mean half-life was 23·9 h (SD 14·0) in the MTD group. Some suggestion of clinical activity was noted in 23 (49%) of 47 patients with haematological malignancies. Based on these results, the recommended phase 2 dose was 200 mg or lower once daily. Based on these findings, PF-04449913 is being tested in phase 2 studies in patients with myelodysplastic syndrome, acute myeloid leukaemia, and myelofibrosis. Pfizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

ClinicalTrials.gov

2016-05-04

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Hematopoietic/Lymphoid Cancer; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

Drinking patterns and beverage preferences of liver cirrhosis patients in Mexico.

PubMed

Campollo, O; Martínez, M D; Valencia, J J; Segura-Ortega, J

2001-02-01

The purpose of this study was to investigate the pattern of alcoholism in a special group of alcoholics (alcoholic cirrhotics) in a hospital-based population in west central Mexico and assess the role of regional spirits such as tequila. A complete alcohol drinking history and a structured questionnaire directed at investigating the pattern of alcohol consumption was applied to 124 adult patients with chronic liver disease caused by alcohol during January 1995 to January 1996. The mean age of onset was 27 +/- 3 years in women and 18 +/- 0.5 years in men. The mean alcohol intake per week was 749 +/- 192 g for women and 1113 +/- 151 g for men. On average, patients consumed alcohol for a mean of 24.5 years. The overall patient drinking preference was for tequila followed by 96 degree Gay Lusac (G.L.), alcohol, and beer. In a subset of 70 patients three phases of alcoholism could be identified (prealcoholic, critical, and chronic). Each phase had a mean duration of at least 11 years. Beer was the dominant beverage in the prealcoholic phase while tequila was consumed more often in the other phases. In the critical phase of alcoholism an average of 337 g of alcohol were consumed per week and in the chronic phase 1765 g/week. Tequila was the overall preferred beverage in this group of alcoholics. Other beverages included beer and straight alcohol with a clear trend from less to higher concentration of alcohol throughout the drinking history. Subtle gender differences in the patterns of alcoholism may be suspected. In this group of patients the role of tequila drinking is highlighted.

Computers in the treatment of chronic aphasia.

PubMed

Katz, Richard C

2010-02-01

Computers and related technology can increase the amount of treatment received by adults with chronic aphasia. Computers used in treatment, however, are only valuable to the patient if the intervention is efficacious. Real and potential applications of computer technology are discussed in the context of three roles of computerized aphasia treatment for adults with chronic aphasia. Pertinent studies regarding Phases 1 and 2 are briefly described. The only Phase 3 study of efficacy of computerized aphasia treatment is more fully described and its implications discussed.

Dasatinib 100 mg Once Daily Minimizes the Occurrence of Pleural Effusion in Patients With Chronic Myeloid Leukemia in Chronic Phase and Efficacy Is Unaffected in Patients who Develop Pleural Effusion

PubMed Central

Porkka, Kimmo; Khoury, H. Jean; Paquette, Ronald L.; Matloub, Yousif; Sinha, Ritwik; Cortes, Jorge E.

2014-01-01

BACKGROUND Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily). METHODS To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed. RESULTS With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. CONCLUSIONS Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy. PMID:19924787

Treating the chronic-phase chronic myeloid leukemia patient: which TKI, when to switch and when to stop?

PubMed

Patel, Ami B; Wilds, Brandon W; Deininger, Michael W

2017-07-01

With the discovery of imatinib mesylate nearly 20 years ago, tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has served as a paradigm of success for targeted drug therapy in cancer. Several new TKIs for CML have been approved over the last two decades that exhibit improved potency over imatinib and have different off-target profiles, providing options for individualized therapy selection. Areas covered: Current management of chronic phase CML, including guidance on the sequential use of imatinib and newer-generation TKIs and evolving treatment strategies such as TKI discontinuation. Relevant literature was identified by searching biomedical databases (i.e. PubMed) for primary research material. Expert commentary: Although survival outcomes have drastically improved for CML patients, treatment for CML has grown more complex with the introduction of next-generation TKIs and the advent of treatment-free remissions (TFR). Goals of therapy have shifted accordingly, with increased focus on improving quality of life, managing patient expectations and optimizing patient adherence.

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: study by the Nagasaki CML Study Group.

PubMed

Itonaga, Hidehiro; Tsushima, Hideki; Imanishi, Daisuke; Hata, Tomoko; Doi, Yuko; Mori, Sayaka; Sasaki, Daisuke; Hasegawa, Hiroo; Matsuo, Emi; Nakashima, Jun; Kato, Takeharu; Horai, Makiko; Taguchi, Masataka; Matsuo, Masatoshi; Taniguchi, Hiroaki; Makiyama, Junnya; Sato, Shinya; Horio, Kensuke; Ando, Koji; Moriwaki, Yuji; Sawayama, Yasushi; Ogawa, Daisuke; Yamasaki, Reishi; Takasaki, Yumi; Imaizumi, Yoshitaka; Taguchi, Jun; Kawaguchi, Yasuhisa; Yoshida, Shinichiro; Joh, Tatsuro; Moriuchi, Yukiyoshi; Nonaka, Hiroaki; Soda, Hisashi; Fukushima, Takuya; Nagai, Kazuhiro; Kamihira, Shimeru; Tomonaga, Masao; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-01-01

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia.

PubMed

Cramer, Paula; von Tresckow, Julia; Bahlo, Jasmin; Engelke, Anja; Langerbeins, Petra; Fink, Anna-Maria; Fischer, Kirsten; Wendtner, Clemens-Martin; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

2018-03-01

Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity. This strategy represents a new era of chronic lymphocytic leukemia therapy where chemotherapy is increasingly replaced by targeted agents and treatment duration is tailored to the patient's individual tumor load and response.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sio, Terence T.; Department of Radiation Oncology, Mayo Clinic, Scottsdale, Arizona; Lin, Huei-Kai

Purpose: We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, than patients treated with intensity modulated photon therapy (IMRT). Methods and Materials: Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms andmore » the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities. Results: PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P<.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (±standard deviation) top 5 MDASI scores were 5.15 ± 2.66 for IMPT versus 6.58 ± 1.98 for IMRT (P=.013). Conclusions: According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors.« less

The influence of a biopsychosocial educational internet-based intervention on pain, dysfunction, quality of life, and pain cognition in chronic low back pain patients in primary care: a mixed methods approach.

PubMed

Valenzuela-Pascual, Fran; Molina, Fidel; Corbi, Francisco; Blanco-Blanco, Joan; Gil, Rosa M; Soler-Gonzalez, Jorge

2015-11-23

Low back pain is the highest reported musculoskeletal problem worldwide. Up to 90 % of patients with low back pain have no clear explanation for the source and origin of their pain. These individuals commonly receive a diagnosis of non-specific low back pain. Patient education is a way to provide information and advice aimed at changing patients' cognition and knowledge about their chronic state through the reduction of fear of anticipatory outcomes and the resumption of normal activities. Information technology and the expedited communication processes associated with this technology can be used to deliver health care information to patients. Hence, this technology and its ability to deliver life-changing information has grown as a powerful and alternative health promotion tool. Several studies have demonstrated that websites can change and improve chronic patients' knowledge and have a positive impact on patients' attitudes and behaviors. The aim of this project is to identify chronic low back pain patients' beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques. This study has a mixed-method sequential exploratory design. The participants are chronic low back pain patients between 18-65 years of age who are attending a primary care setting. For the qualitative phase, subjects will be contacted by their family physician and invited to participate in a personal semi-structured interview. The quantitative phase will be a randomized controlled trial. Subjects will be randomly allocated using a simple random sample technique. The intervention group will be provided access to the web site where they will find information related to their chronic low back pain. This information will be provided in different formats. All of this material will be based on the information obtained in the qualitative phase. The control group will follow conventional treatment provided by their family physician. The main outcome of this project is to identify chronic low back pain patients' beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques. ClinicalTrials.gov NCT02369120 Date: 02/20/2015.

BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.

PubMed

Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

2015-09-01

BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.

Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial.

PubMed

Saussele, Susanne; Richter, Johan; Guilhot, Joelle; Gruber, Franz X; Hjorth-Hansen, Henrik; Almeida, Antonio; Janssen, Jeroen J W M; Mayer, Jiri; Koskenvesa, Perttu; Panayiotidis, Panayiotis; Olsson-Strömberg, Ulla; Martinez-Lopez, Joaquin; Rousselot, Philippe; Vestergaard, Hanne; Ehrencrona, Hans; Kairisto, Veli; Machová Poláková, Katerina; Müller, Martin C; Mustjoki, Satu; Berger, Marc G; Fabarius, Alice; Hofmann, Wolf-Karsten; Hochhaus, Andreas; Pfirrmann, Markus; Mahon, Francois-Xavier

2018-06-01

Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres in 11 countries. Eligible patients had chronic-phase chronic myeloid leukaemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year. The primary endpoint was molecular relapse-free survival, defined by loss of major molecular response (MMR; >0·1% BCR-ABL1 on the International Scale) and assessed in all patients with at least one molecular result. Secondary endpoints were a prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples and the cost impact of stopping TKI therapy. We considered loss of haematological response, progress to accelerated-phase chronic myeloid leukaemia, or blast crisis as serious adverse events. This study presents the results of the prespecified interim analysis, which was done after the 6-month molecular relapse-free survival status was known for 200 patients. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01596114. Between May 30, 2012, and Dec 3, 2014, we assessed 868 patients with chronic myeloid leukaemia for eligibility, of whom 758 were enrolled. Median follow-up of the 755 patients evaluable for molecular response was 27 months (IQR 21-34). Molecular relapse-free survival for these patients was 61% (95% CI 57-64) at 6 months and 50% (46-54) at 24 months. Of these 755 patients, 371 (49%) lost MMR after TKI discontinuation, four (1%) died while in MMR for reasons unrelated to chronic myeloid leukaemia (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted TKI therapy while in MMR. A further six (1%) patients died in chronic-phase chronic myeloid leukaemia after loss of MMR and re-initiation of TKI therapy for reasons unrelated to chronic myeloid leukaemia, and two (<1%) patients lost MMR despite restarting TKI therapy. In the prognostic analysis in 405 patients who received imatinib as first-line treatment (learning sample), longer treatment duration (odds ratio [OR] per year 1·14 [95% CI 1·05-1·23]; p=0·0010) and longer deep molecular response durations (1·13 [1·04-1·23]; p=0·0032) were associated with increasing probability of MMR maintenance at 6 months. The OR for deep molecular response duration was replicated in the validation sample consisting of 171 patients treated with any TKI as first-line treatment, although the association was not significant (1·13 [0·98-1·29]; p=0·08). TKI discontinuation was associated with substantial cost savings (an estimated €22 million). No serious adverse events were reported. Patients with chronic myeloid leukaemia who have achieved deep molecular responses have good molecular relapse-free survival. Such patients should be considered for TKI discontinuation, particularly those who have been in deep molecular response for a long time. Stopping treatment could spare patients from treatment-induced side-effects and reduce health expenditure. ELN Foundation and France National Cancer Institute. Copyright © 2018 Elsevier Ltd. All rights reserved.

Imatinib 800 mg daily induces deeper molecular responses than imatinib 400 mg daily: results of SWOG S0325, an intergroup randomized PHASE II trial in newly diagnosed chronic phase chronic myeloid leukaemia.

PubMed

Deininger, Michael W; Kopecky, Kenneth J; Radich, Jerald P; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D; Tallman, Martin; Wadleigh, Martha; Larson, Richard A; Lipton, Jeffrey H; Slovak, Marilyn L; Appelbaum, Frederick R; Druker, Brian J

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukaemia (CP-CML) is 400 mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematological and cytogenetic response to IM400 vs. imatinib 400 mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P = 0·038; 3-log reduction: 53% vs. 35%, P = 0·049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2·9-fold lower than in the IM400 arm (P = 0·010). Complete haematological response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P = 0·040). Grade 3-4 toxicities were more common for IM800 (58% vs. 31%, P = 0·0007), and were most commonly haematological. Few patients have relapsed, progressed or died, but both progression-free (P = 0·048) and relapse-free (P = 0·031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper MRs than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. © 2013 John Wiley & Sons Ltd.

Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study.

PubMed

Gaul, Charly; Magis, Delphine; Liebler, Eric; Straube, Andreas

2017-12-01

In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study. After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P < 0.02). Attack frequencies in the nVNS + SoC group were significantly lower at all study time points than they were at baseline (P < 0.05). Response rates were significantly greater with nVNS + SoC than with SoC alone when response was defined as attack frequency reductions of ≥25%, ≥50%, and ≥75% from baseline (≥25% and ≥50%, P < 0.001; ≥75%, P = 0.009). The 100% response rate was 8% with nVNS + SoC and 0% with SoC alone. Prophylactic nVNS led to rapid, significant, and sustained reductions in chronic cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher ≥25%, ≥50%, and ≥75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache.

Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial.

PubMed

Cortes, Jorge E; De Souza, Carmino Antonio; Ayala, Manuel; Lopez, Jose Luis; Bullorsky, Eduardo; Shah, Sandip; Huang, Xiaojun; Babu, K Govind; Abdulkadyrov, Kudrat; de Oliveira, José Salvador Rodrigues; Shen, Zhi-Xiang; Sacha, Tomasz; Bendit, Israel; Liang, Zhizhou; Owugah, Tina; Szczudlo, Tomasz; Khanna, Sadhvi; Fellague-Chebra, Rafik; le Coutre, Philipp D

2016-12-01

Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0-2. Before enrolment, all patients had received 3-18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months' follow-up. This study is registered with ClinicalTrials.gov (NCT00802841). Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95·18% CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 7·9% in favour of nilotinib; 95% CI -6·2 to 22·0, p=0·31). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0·058). Grade 3-4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related. While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included. Novartis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atrophic inferior vena cava is a marker of chronicity of intra-filter and inferior vena cava thrombosis: based on CT findings.

PubMed

Chen, Liang; Shi, Wanyin; Gu, Jianping; He, Xu; Lou, Wensheng

2018-04-11

A permanently indwelling filter in the inferior vena cava (IVC) may induce caval thrombosis, which could develop and evolve from an acute to a chronic phase. The differential diagnosis of acute and chronic thromboses determines the treatment strategy. The role of computed tomography (CT) in diagnosing acute and chronic intra-filter and IVC thromboses has not been well established. This retrospective study summarizes the CT signs that indicate acute and chronic phases of intra-filter and IVC thromboses. This study included eight patients who developed a lower-extremity deep venous thrombosis (DVT) and were treated with intracaval filter placement as an alternative to anticoagulation and thrombolysis. During the follow-up, all patients developed an intra-filter thrombosis in the IVC confirmed by CT and/or CT venography (CTV). Demographic and CT data of all patients during the follow-up period were collected for analysis. All patients had normal-appearing IVCs prior to filter placement, as shown on trans-femoral venography. Eight filters (five TrapEase, three OptEase) were placed in the eight IVCs, respectively. Subsequently, IVC-CT or CTV revealed acute intra-filter or IVC thrombosis in all eight patients, manifesting as an intracaval filling defect and thickened IVC wall. Filter protrusion and secondary caval atrophy seen on CT indicated a chronically occluded IVC. IVC thrombosis may result from filter placement. The chronicity of caval thrombotic occlusion is likely to be associated with filter protrusion and secondary IVC atrophy revealed on CT scans.

A nurse-led model of chronic disease management in general practice: Patients' perspectives.

PubMed

Young, Jacqueline; Eley, Diann; Patterson, Elizabeth; Turner, Catherine

2016-12-01

Evidence suggests that current models of chronic disease management within general practice are not effective in meeting the needs of the community. The objective of this article is to examine patients' perceptions of a nurse-led collaborative model of care trialled in three general practices in Australia. This article reports on the second phase of a mixed-methods study in which semi-structured interviews with purposively selected patients were conducted to elicit information about their perceptions of nurse-led care. Three themes emerged from the data - time, ambiance and dimensions of the nurse role. The results suggest that general practice nurses had a positive impact on patients' ability to manage their chronic disease. This infers that there is scope for general practice nurses to expand their role in chronic disease management to assist patients to better self-manage their chronic diseases.

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia

PubMed Central

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P.; Snyder, David S.; Khoury, Jean; Bhalla, Kapil N.; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C.; Rutkoski, Thomas J.; Smith, Bryan D.; Flynn, Daniel L.; Kantarjian, Hagop M.; Rosen, Oliver; Van Etten, Richard A.

2017-01-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5′-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib (clinicaltrials.gov Identifier:00827138). PMID:27927766

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia.

PubMed

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P; Snyder, David S; Khoury, Jean; Bhalla, Kapil N; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C; Rutkoski, Thomas J; Smith, Bryan D; Flynn, Daniel L; Kantarjian, Hagop M; Rosen, Oliver; Van Etten, Richard A

2017-03-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5'-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib ( clinicaltrials.gov Identifier:00827138 ). Copyright© Ferrata Storti Foundation.

Low educational level but not low income impairs the achievement of cytogenetic remission in chronic myeloid leukemia patients treated with imatinib in Brazil.

PubMed

Rego, Monica Napoleão Fortes; Metze, Konradin; Lorand-Metze, Irene

2015-05-01

In Brazil, imatinib mesylate is supplied as the first-line therapy for chronic myeloid leukemia in the chronic phase through the public universal healthcare program, Sistema Único de Saúde (SUS). We studied the socio-demographic factors that influenced therapy success in a population in the northeast region of Brazil. Patients with chronic myeloid leukemia from the state of Piauí were treated in only one reference center. Diagnosis was based on WHO 2008 criteria. Risk was assessed by Sokal, Hasford and EUTOS scores. Patients received 400 mg imatinib daily. We studied the influence of the following factors on the achievement of complete cytogenetic response within one year of treatment: age, clinical risk category, time interval between diagnosis and the start of imatinib treatment, geographic distance from the patient's home to the hospital, years of formal education and monthly income. Among 103 patients studied, the median age was 42 years; 65% of the patients had 2-9 years of formal education, and the median monthly income was approximately 100 US$. Imatinib was started in the first year after diagnosis (early chronic phase) in 69 patients. After 12 months of treatment, 68 patients had a complete cytogenetic response. The Hasford score, delay to start imatinib and years of formal education influenced the attainment of a complete cytogenetic response, whereas income and the distance from the home to the healthcare facility did not. Patients require additional healthcare information to better understand the importance of long-term oral anticancer treatment and to improve their compliance with the treatment.

Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

PubMed Central

Jabbour, Elias; Saglio, Giuseppe; Steegmann, Juan Luis; Shah, Neil P.; Boqué, Concepción; Chuah, Charles; Pavlovsky, Carolina; Mayer, Jiří; Cortes, Jorge; Baccarani, Michele; Kim, Dong-Wook; Bradley-Garelik, M. Brigid; Mohamed, Hesham; Wildgust, Mark; Hochhaus, Andreas

2014-01-01

This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov as NCT00481247. PMID:24311723

Gallbladder emptying to endogenous and exogenous stimulation in chronic pancreatitis patients.

PubMed

Meguro, T; Shimosegawa, T; Kashimura, J; Kikuchi, Y; Koizumi, M; Toyota, T

1994-02-01

The present study was designed to analyze the underlying mechanism of gallbladder motor disturbance in chronic pancreatitis patients. Gallbladder emptying to endogenous (oral test meal, Daiyan 13 g) and exogenous stimulation (iv cerulein, 30 ng/kg for 5 min) was examined by real-time ultrasonography in 12 patients with chronic pancreatitis and 10 normal subjects (controls). Plasma cholecystokinin levels during the endogenous stimulation were measured by bioassay. In chronic pancreatitis patients compared with controls, the fasting gallbladder volume was significantly increased (29.5 +/- 2.2 vs. 21.5 +/- 2.8 ml), whereas the gallbladder emptying (percent change of the basal volume) to oral test meal was significantly decreased. Neither cholecystokinin secretion induced by the test meal, nor the gallbladder emptying response to intravenous cerulein, differed significantly between the two groups. However, when chronic pancreatitis patients were divided according to pathogenesis, it became clear that gallbladder emptying to intravenous cerulein was significantly greater in patients with alcoholic chronic pancreatitis than in patients with idiopathic pancreatitis. Gallbladder emptying during the intestinal phase is generally reduced in patients with chronic pancreatitis, but gallbladder responsiveness to exogenous stimulation might be heterogeneous according to the pathogenesis.

Donor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases

ClinicalTrials.gov

2017-03-29

Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Juvenile Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Childhood Acute Lymphoblastic Leukemia; Secondary Myelodysplastic Syndromes

Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

PubMed

Weir, Matthew R; Bakris, George L; Gross, Coleman; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Yuan, Jinwei; Berman, Lance; Williams, Gordon H

2016-09-01

Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.

PubMed

Wiernik, P H; Gordon, L I; Oken, M M; Harris, J E; O'Connell, M J

1999-10-01

Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. We, therefore, tested this agent for activity against chronic lymphocytic leukemia (CLL) in this phase II study. Mitoguazone, 500 mg/M2 was given intravenously weekly to 13 patients with relapsed or refractory, previously treated Rai stages 2-4 CLL. There were no complete or partial responses as judged by standard criteria. Toxicity was acceptable. Mitoguazone in the dose and schedule employed in this study has no significant activity as a single agent in patients with relapsed or refractory CLL.

Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease.

PubMed

Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

2015-12-01

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

White matter lesional predictors of chronic visual neglect: a longitudinal study

PubMed Central

Lunven, Marine; Thiebaut De Schotten, Michel; Bourlon, Clémence; Duret, Christophe; Migliaccio, Raffaella; Rode, Gilles

2015-01-01

Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient’s lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect. PMID:25609686

Increasing methylation of the calcitonin gene during disease progression in sequential samples from CML patients.

PubMed

Mills, K I; Guinn, B A; Walsh, V A; Burnett, A K

1996-09-01

In chronic myeloid leukaemia (CML), disease progression from the initial chronic phase to the acute phase or blast crisis has previously been shown to be correlated with progressive increases in hyper-methylation of the calcitonin gene, located at chromosome 11p15. However, sequential studies of individual patients were not performed in these investigations. We have analysed 44 samples from nine patients with typical Philadelphia chromosome positive CML throughout their disease progression to determine the methylation state of the calcitonin gene at these time points. Densitometry was used to quantitate the ratio of the normal 2.0 kb Hpa II fragments, indicating normal methylation status of the gene, compared to the intensity of the abnormal, hyper-methylated, 2.6-3.1 kb Hpa II fragments. We found a gradual increase in the ratio of methylated:unmethylated calcitonin gene during chronic phase with a dramatic rise at blast crisis. Further, the ratio of the abnormal hypermethylated 3.1 kb fragments to the methylated 2.6 kb fragment resulted in the identification of a clonal expansion of abnormally methylated cells. This expansion of cells with hypermethylation of the calcitonin gene during chronic phase was shown to coincide with the presence of a mutation in the p53 gene. The data presented in this study would suggest that an increased methylation status of the calcitonin gene during disease progression may indicate the expansion of abnormal blast cell populations and subsequent progression to blast crisis.

Pharyngeal swallowing phase and chronic cough

PubMed Central

Drozdz, Daniela Rejane Constantino; Costa, Cintia Conceição; Jesus, Paulo Roberto de Oliveira; Trindade, Mateus Silva; Weiss, Guilherme; Neto, Abdias Baptista M.; da Silva, Ana Maria T.; Mancopes, Renata

2012-01-01

Summary Introduction: The act of swallowing depends on a complex and dynamic process which uses common structures to the act of breathing; respiratory problems can cause swallowing difficulties. Aim: To assess the swallowing pharyngeal phase in patients with chronic cough. Method: Retrospective study with 15 patients of both genders, patients with chronic cough and risk factors for aspiration defined by the pneumologic diagnosis. The patients were submitted to anamnesis on complaints related to swallowing, chewing and breathing, or related to food and to videofluoroscopic examination. Results: It was observed that 33.3% had normal and functional swallowing, being the last one of most prevalence. The mild dysphagia was observed in 20% of the patients, the mild to moderate dysphagia in 6.7% of them. In relation to the Rosenbek scale, 73.3% of patients presented degree 1, 6.7% presented degrees 2 and 3, and 13.3% presented degree 8. The most found pathology was the chronic cough with 40%, followed by asthma with 20%; 69.2% of patients presented stasis and of these, five used protection maneuvers, of these, seven were effective and only three were used in the presence of stasis. The most used maneuver was the multiple swallowing, being effective in 100%. Conclusion: There are peculiarities in the patients' swallowing with chronic cough that, although not presenting complaints relating to swallowing, it presents an important aspiration risk due to the presence of changes in breathing pattern that can intervene in the coordination between breathing and swallowing, which is essential to protect the lower airway. PMID:25991980

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial.

PubMed

O'Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

2014-01-01

Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one developed grade 4 thrombocytopenia. After a median follow-up of 22.1 months (IQR 18.4-23.2), 22 (71%) of 31 patients achieved an objective response (95% CI 52.0-85.8); four patients (13%) had a complete response, one patient (3%) had a nodular partial response, and 17 (55%) patients had a partial response. The safety and activity of ibrutinib in elderly, previously untreated patients with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is encouraging, and merits further investigation in phase 3 trials. Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

ClinicalTrials.gov

2018-06-13

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

Cancer.gov

A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Impact of ELN recommendations in the management of first-line treated chronic myeloid leukaemia patients: a French cross-sectional study.

PubMed

Etienne, Gabriel; Huguet, Francoise; Guerci-Bresler, Agnès; Nicolini, Franck E; Maloisel, Frédéric; Coiteux, Valérie; Dauriac, Charles; Carpentier, Nathalie; Bourdeix, Isabelle; Tulliez, Michel; Cony-Makhoul, Pascale

2016-07-01

The availability of tyrosine kinase inhibitors has extended therapeutic options for chronic myeloid leukaemia (CML) patients. Monitoring recommendations and clinical response goals have recently been updated. The objective of this study was to describe the profile of CML patients in chronic phase currently receiving first-line therapy, including treatment, monitoring and response kinetics. A multicentre, cross-sectional, epidemiological survey in unselected chronic phase CML patients in France attending consultations during a one-month period was performed. 438 of 697 (62·8%) reported patients were currently receiving first-line treatment and were analysed. Imatinib was the most frequently received treatment (72·4% of patients). Retrospective cytogenetic and molecular assessments at 3, 6, 12 or 18 months were available in 88·4% of patients. At the 12-month assessment, 32·2% were not in major molecular response (MMR). At last assessment, among 355 patients with duration of treatment ≥ 12 months, 91·5% had achieved MMR and 66·5% were in deep molecular response. This study, performed in everyday practice population of CML patients, suggests that monitoring of molecular responses in real-life practice is aligned with European LeukaemiaNet recommendations. The majority of patients still receiving first-line treatment are in optimal response, with a few being classified as in the warning area or responding to failure. © 2016 John Wiley & Sons Ltd.

Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.

PubMed

Olin, Jacqueline L; Griffiths, Carrie L; Smith, Morgan B

2017-01-01

Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.

Family needs in the chronic phase after severe brain injury in Denmark.

PubMed

Doser, Karoline; Norup, Anne

2014-01-01

This preliminary study aimed at investigating (1) changes in the status of family members between time of injury and follow-up in the chronic phase and (2) the most important needs within the family in the chronic phase and whether the needs were perceived as met. The sample comprised 42 relatives (76% female, mean age = 53 years) of patients with severe brain injury, who had received intensive sub-acute rehabilitation. The relatives were contacted in the chronic phase after brain injury. A set of questions about demographics and time spent caregiving for the patient was completed. The relatives completed the revised version of the Family Needs Questionnaire, a questionnaire consisting of 37 items related to different needs following brain injury. Significant changes in status were found in employment (z = -3.464, p = 0.001) and co-habitation (z = -3.317, p = 0.001). The sub-scale 'Health Information' (Mean = 3.50, SD = 0.73) had the highest mean importance rating, whereas the sub-scale 'Emotional support' (Mean = 3.07, SD = 0.79) had the lowest. When combining importance and met ratings, it was found that the five most important needs were only met in 41-50% of the total sample. Occupational and co-habitation status of the relatives was significantly affected by brain injury. A high number of relatives reported family needs not satisfied in the chronic phase. This requires an interventional approach for families to get these needs fulfilled individually, even after rehabilitation.

[Treatment of non-cirrhotic, non-tumoural portal vein thrombosis].

PubMed

Llop, Elba; Seijo, Susana

2016-01-01

Thrombosis of the splenoportal axis not associated with liver cirrhosis or neoplasms is a rare disease whose prevalence ranges from 0.7 to 3.7 per 100,000 inhabitants. However, this entity is the second most common cause of portal hypertension. Prothrombotic factors are present as an underlying cause in up to 70% of patients and local factors in 10-50%. The coexistence of several etiological factors is frequent. Clinical presentation may be acute or chronic (portal cavernomatosis). The acute phase can present as abdominal pain, nausea, vomiting, fever, rectorrhagia, intestinal congestion, and ischemia. In this phase, early initiation of anticoagulation is essential to achieve portal vein recanalization and thus improve patient prognosis. In the chronic phase, symptoms are due to portal hypertension syndrome. In this phase, the aim of treatment is to treat or prevent the complications of portal hypertension. Anticoagulation is reserved to patients with a proven underlying thrombophilic factor. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Sudden blast phase in chronic myeloid leukemia developed during nilotinib therapy after major molecular response was achieved.

PubMed

Okada, Yosuke; Sato, Ken; Kobayashi, Shinichi; Nagao, Shigeki; Takano, Kosuke; Teramoto, Masahiro; Tachi, Noriaki; Kawamura, Toshikuni; Horiuchi, Toshikatsu; Kato, Shoichiro; Saga, Reina; Maekawa, Takaaki; Yamamura, Takeshi; Watanabe, Junichi; Kobayashi, Ayako; Kimura, Fumihiko

2018-04-01

Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.

Complex adaptive chronic care - typologies of patient journey: a case study.

PubMed

Martin, Carmel M; Grady, Deirdre; Deaconking, Susan; McMahon, Catherine; Zarabzadeh, Atieh; O'Shea, Brendan

2011-06-01

Complex adaptive chronic care (CACC) is a framework based upon complex adaptive systems' theory developed to address different stages in the patient journey in chronic illness. Simple, complicated, complex and chaotic phases are proposed as diagnostic types. To categorize phases of the patient journey and evaluate their utility as diagnostic typologies. A qualitative case study of two cohorts, identified as being at risk of avoidable hospitalization: 12 patients monitored to establish typologies, followed by 46 patients to validate the typologies. Patients were recruited from a general practitioner out-of-hours service. Self-rated health, medical and psychological health, social support, environmental concerns, medication adherence and health service use were monitored with phone calls made 3-5 times per week for an average of 4 weeks. Analysis techniques included frequency distributions, coding and categorization of patients' longitudinal data using a CACC framework. Twelve and 46 patients, mean age 69 years, were monitored for average of 28 days in cohorts 1 and 2 respectively. Cohorts 1 and 2 patient journeys were categorized as being: stable complex 66.66% vs. 67.4%, unstable complex 25% vs. 26.08% and unstable complex chaotic 8.3% vs. 6.52% respectively. An average of 0.48, 0.75 and 2 interventions per person were provided in the stable, unstable and chaotic journeys. Instability was related to complex interactions between illness, social support, environment, as well as medication and medical care issues. Longitudinal patient journeys encompass different phases with characteristic dynamics and are likely to require different interventions and strategies - thus being 'adaptive' to the changing complex dynamics of the patient's illness and care needs. CACC journey types provide a clinical tool for health professionals to focus time and care interventions in response to patterns of instability in multiple domains in chronic illness care. © 2011 Blackwell Publishing Ltd.

Bug Smash, Bug Splash: A Case Report of an Unusual Transmission of American Trypanosomiasis with a Brief Review of the Literature

PubMed Central

Navarrete-Sandoval, Rafael Hernán; Servín-Rojas, Maximiliano

2016-01-01

Patient: Male, 44 Final Diagnosis: Acute phase Chagas disease Symptoms: Fever • headache • periorbital oedema Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. Case Report: We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa. Conclusions: The diagnosis of Chagas disease is made by the direct visualization of the parasite in blood smears during the acute phase of the disease; during the chronic phase of the disease the diagnosis is made by the detection of IgG antibodies. Parasitological cure can be achieved in up to 80% of the cases in acute phase of the disease, in contrast with less than 30% during the chronic phase. PMID:28031550

Considering baseline factors and early response rates to optimize therapy for chronic myeloid leukemia in chronic phase.

PubMed

Akard, Luke P; Bixby, Dale

2016-05-01

Multiple BCR-ABL tyrosine kinase inhibitors (TKIs) are available for the treatment of chronic myeloid leukemia in chronic phase (CML-CP), and several baseline and on-treatment predictive factors have been identified that can be used to help guide TKI selection for individual patients. In particular, early molecular response (EMR; BCR-ABL ≤10% on the International Scale at 3 months) has become an accepted benchmark for evaluating whether patients with CML-CP are responding optimally to frontline TKI therapy. Failure to achieve EMR is considered an inadequate initial response according to the National Comprehensive Cancer Network guidelines and a warning response according to the European LeukemiaNet recommendations. Here we review data supporting the importance of achieving EMR for improving patients' long-term outcomes and discuss key considerations for selecting a frontline TKI in light of these data. Because a higher proportion of patients achieve EMR with second-generation TKIs such as nilotinib and dasatinib than with imatinib, these TKIs may be preferable for many patients, particularly those with known negative prognostic factors at baseline. We also discuss other considerations for frontline TKI choice, including toxicities, cost-effectiveness, and the emerging goals of deep molecular response and treatment-free remission.

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial.

PubMed

Cortes, Jorge E; Saglio, Giuseppe; Kantarjian, Hagop M; Baccarani, Michele; Mayer, Jiří; Boqué, Concepción; Shah, Neil P; Chuah, Charles; Casanova, Luis; Bradley-Garelik, Brigid; Manos, George; Hochhaus, Andreas

2016-07-10

We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP. © 2016 by American Society of Clinical Oncology.

The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate.

PubMed

Lee, Sung-Eun; Choi, Soo Young; Bang, Ju-Hee; Kim, Soo-Hyun; Jang, Eun-Jung; Byeun, Ji-Young; Park, Jin Eok; Jeon, Hye-Rim; Oh, Yun Jeong; Kim, Myungshin; Kim, Dong-Wook

2012-11-01

The aim of this study was to evaluate the long-term clinical significance of an additional chromosomal abnormality (ACA), variant Philadelphia chromosome (vPh) at diagnosis, and newly developed other chromosomal abnormalities (OCA) in patients with chronic myeloid leukemia (CML) on imatinib (IM) therapy. Sequential cytogenetic data from 281 consecutive new chronic phase CML patients were analyzed. With a median follow-up of 78.6 months, the 22 patients with vPh (P = 0.034) or ACA (P = 0.034) at diagnosis had more events of IM failure than did the patients with a standard Ph. The 5-year overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) rates for patients with vPh at diagnosis were 77.8%, 75.0%, and 53.3%, respectively; for patients with ACA at diagnosis, 100%, 66.3%, and 52.1%, respectively; and for patients with a standard Ph, 96.0%, 91.3%, and 83.7%, respectively. During IM therapy, eight patients developed an OCA, which had no impact on outcomes as a time-dependent covariate in our Cox proportional hazards regression models. This study showed that vPh was associated with poor OS and FFS and that ACA had adverse effects on EFS and FFS. In addition, no OCA, except monosomy 7, had any prognostic impact, suggesting that the development of OCA may not require a change in treatment strategy. Copyright © 2012 Elsevier Inc. All rights reserved.

Transplantation from haploidentical donor is not inferior to that from identical sibling donor for patients with chronic myeloid leukemia in blast crisis or chronic phase from blast crisis.

PubMed

Ma, Yan-Ru; Huang, Xiao-Jun; Xu, Zheng-Li; Liu, Kai-Yan; Chen, Huan; Zhang, Xiao-Hui; Han, Wei; Chen, Yu-Hong; Wang, Feng-Rong; Wang, Jing-Zhi; Wang, Yu; Chen, Yao; Yan, Chen-Hua; Xu, Lan-Ping

2016-09-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for chronic myeloid leukemia (CML) patients in blast crisis (BC), and haploidentical donors (HID) are immediately available for most patients. We compared the outcomes of HID transplantation with those of matched related donor (MRD) transplantation in a cohort study. A total of 90 consecutive patients who received allogeneic HSCT because of CML-BC were investigated retrospectively. A total of 67 patients underwent transplantation from HID and 23 from MRD. Survival outcomes were compared between the two cohorts. Of the 90 patients, 86 patients were engrafted. Three-year overall survival (OS) and relapse-free survival (RFS) were comparable between HID and MRD recipients (OS: 60.0% vs 55.3%, respectively, P=.580; RFS: 51.1% vs 47.8%, respectively, P=.512). Three-year incidences of transplant-related mortality (TRM) and relapse did not differ between HID and MRD recipients (relapse: 21.0% vs 26.1%, respectively, P=.626; TRM: 27.9% vs 26.1%, respectively, P=.937). In multivariate analyses, previous chemotherapy history and not achieving CHR before HSCT are independent adverse predictors of OS. For CML-blast crisis or chronic phase from blast crisis patients, HID transplantation achieves comparable survival to MRD transplantation. HID donors can be regarded as regular donors for these special patients at selected centers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cognitive Behavioral Analysis System of Psychotherapy and Brief Supportive Psychotherapy for Augmentation of Antidepressant Nonresponse in Chronic Depression

PubMed Central

Kocsis, James H.; Gelenberg, Alan J.; Rothbaum, Barbara O.; Klein, Daniel N.; Trivedi, Madhukar H.; Manber, Rachel; Keller, Martin B.; Leon, Andrew C.; Wisniewski, Steven R.; Arnow, Bruce A.; Markowitz, John C.; Thase, Michael E.

2012-01-01

Context Previous studies have found that few chronically depressed patients remit with antidepressant medications alone. Objective To determine the role of adjunctive psychotherapy in the treatment of chronically depressed patients with less than complete response to an initial medication trial. Design This trial compared 12 weeks of (1) continued pharmacotherapy and augmentation with cognitive behavioral analysis system of psychotherapy (CBASP), (2) continued pharmacotherapy and augmentation with brief supportive psychotherapy (BSP), and (3) continued optimized pharmacotherapy (MEDS) alone. We hypothesized that adding CBASP would produce higher rates of response and remission than adding BSP or continuing MEDS alone. Setting Eight academic sites. Participants Chronically depressed patients with a current DSM-IV–defined major depressive episode and persistent depressive symptoms for more than 2 years. Interventions Phase 1 consisted of open-label, algorithm-guided treatment for 12 weeks based on a history of antidepressant response. Patients not achieving remission received next-step pharmacotherapy options with or without adjunctive psychotherapy (phase 2). Individuals undergoing psychotherapy were randomized to receive either CBASP or BSP stratified by phase 1 response, ie, as nonresponders (NRs) or partial responders (PRs). Main Outcome Measures Proportions of remitters, PRs, and NRs and change on Hamilton Scale for Depression (HAM-D) scores. Results In all, 808 participants entered phase 1, of which 491 were classified as NRs or PRs and entered phase 2 (200 received CBASP and MEDS, 195 received BSP and MEDS, and 96 received MEDS only). Mean HAM-D scores dropped from 25.9 to 17.7 in NRs and from 15.2 to 9.9 in PRs. No statistically significant differences emerged among the 3 treatment groups in the proportions of phase 2 remission (15.0%), partial response (22.5%), and non-response (62.5%) or in changes on HAM-D scores. Conclusions Although 37.5% of the participants experienced partial response or remitted in phase 2, neither form of adjunctive psychotherapy significantly improved outcomes over that of a flexible, individualized pharmacotherapy regimen alone. A longitudinal assessment of later-emerging benefits is ongoing. Trial Registration clinicaltrials.gov Identifier: NCT00057551 PMID:19884606

Adherence to follow-up and treatment recommendations in Greek and immigrant patients with chronic hepatitis B in Greece.

PubMed

Voulgaris, Theodoros; Vlachogiannakos, John; Ioannidou, Panagiota; Papageorgiou, Maria-Vasiliki; Zampeli, Evi; Karagiannakis, Dimitrios; Georgiou, Anastasia; Papazoglou, Afroditi; Karamanolis, George; Papatheodoridis, George V

2017-03-01

Immigrants have multiple barriers to access to health care systems. We evaluated the adherence to follow-up and treatment recommendations of chronic hepatitis B virus (HBV) Greek and immigrant patients. In total, 1001 consecutive adult patients with chronic HBV infection who visited our clinics for the first time between 2002 and 2011 were included. All patients born outside Greece were considered immigrants. Diagnosis was considered to be complete if patients could be classified into HBeAg-positive chronic hepatitis B (CHB), inactive carriers, HBeAg-negative CHB, or decompensated cirrhosis. Of the patients, 56% were Greeks and 44% were immigrants. Greeks visited our clinics at a significantly older mean age (50 vs. 35 years, P<0.001) and more frequently with advanced liver disease (11.4 vs. 6.4%, P=0.007). During the first year, Greeks more frequently had several tests and eventually a complete diagnosis (68 vs. 55%, P<0.001). Greeks were more frequently in the phase of HBeAg-negative CHB and less frequently in the phase of inactive carrier or HBeAg-positive CHB, but age was the main determinant for these differences in multivariate analysis. Treatment was initiated more frequently by Greeks than immigrants with treatment indications (86 vs. 65%, P<0.001). Only 30-33% of treated and 4-10% of untreated patients remained under follow-up at year 5, without significant differences between Greeks and immigrants. Adherence to follow-up recommendations is rather poor for all chronic HBV patients. Immigrants are lost more frequently during the first year, but only small proportions of treated and particularly untreated Greek or immigrant patients remain under long-term follow-up.

Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV.

PubMed

Proetel, Ulrike; Pletsch, Nadine; Lauseker, Michael; Müller, Martin C; Hanfstein, Benjamin; Krause, Stefan W; Kalmanti, Lida; Schreiber, Annette; Heim, Dominik; Baerlocher, Gabriela M; Hofmann, Wolf-Karsten; Lange, Elisabeth; Einsele, Hermann; Wernli, Martin; Kremers, Stephan; Schlag, Rudolf; Müller, Lothar; Hänel, Mathias; Link, Hartmut; Hertenstein, Bernd; Pfirrman, Markus; Hochhaus, Andreas; Hasford, Joerg; Hehlmann, Rüdiger; Saußele, Susanne

2014-07-01

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874

Key components of effective collaborative goal setting in the chronic care encounter.

PubMed

Bigi, Sarah

2014-01-01

Collaborative goal setting in patient-provider communication with chronic patients is the phase in which--after collecting the data regarding the patient's health--it is necessary to make a decision regarding the best therapy and behaviors the patient should adopt until the next encounter. Although it is considered a pivotal phase of shared decision making, there remain a few open questions regarding its components and its efficacy: What are the factors that improve or impede agreement on treatment goals and strategies?; What are the 'success conditions' of collaborative goal setting?; How can physicians effectively help patients make their preferences explicit and then co-construct with them informed preferences to help them reach their therapeutic goals? Using the theoretical framework of dialogue types, an approach developed in the field of Argumentation Theory, it will be possible to formulate hypotheses on the success conditions' and effects on patient commitment of collaborative goal setting.

Localizing chronic Q fever: a challenging query

PubMed Central

2013-01-01

Background Chronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed. Methods Fifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded. Results According to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively. Conclusions If chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions. PMID:24004470

Tyrosine kinase inhibition: A therapeutic target for the management of chronic-phase chronic myeloid leukemia

PubMed Central

Jabbour, Elias J; Cortes, Jorge E; Kantarjian, Hagop M

2014-01-01

Chronic myeloid leukemia (CML) is a hematologic neoplasm with a progressive, ultimately terminal, disease course. In most cases, CML arises owing to the aberrant formation of a chimeric gene for a constitutively active tyrosine kinase. Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target transforming the prognosis of patients with CML. New tyrosine kinase inhibitors (TKIs) continue to improve the management of CML, offering alternative options for those resistant to or intolerant of standard TKIs. Here we review the pathobiology of CML and explore emerging strategies to optimize the management of chronic-phase CML, particularly first-line treatment. PMID:24236822

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C

PubMed Central

Belle, Steven H; Fried, Michael W; Afdhal, Nezam; Navarro, Victor J; Hawke, Roy L; Wahed, Abdus S; Doo, Edward; Meyers, Catherine M

2012-01-01

Background Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. Purpose We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. Methods This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. Results Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. Potential limitations Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. Conclusions The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products. PMID:22058086

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C.

PubMed

Reddy, K Rajender; Belle, Steven H; Fried, Michael W; Afdhal, Nezam; Navarro, Victor J; Hawke, Roy L; Wahed, Abdus S; Doo, Edward; Meyers, Catherine M

2012-02-01

Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. POTENTIAL LIMITATIONS: Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products.

Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199).

PubMed

Patel, V M; Balakrishnan, K; Douglas, M; Tibbitts, T; Xu, E Y; Kutok, J L; Ayers, M; Sarkar, A; Guerrieri, R; Wierda, W G; O'Brien, S; Jain, N; Stern, H M; Gandhi, V

2017-09-01

Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma. In CLL, duvelisib monotherapy is associated with high iwCLL (International Workshop on Chronic Lymphocytic Leukemia) and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene expression studies (RNAseq, Nanostring, Affymetrix array and real-time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes. In concert with induction of transcript levels, reverse phase protein arrays and immunoblots confirmed increase at the protein level. The BCL2 inhibitor venetoclax induced greater apoptosis in ex vivo-cultured CLL cells obtained from patients on duvelisib compared with pre-treatment CLL cells from the same patients. In vitro combination of duvelisib and venetoclax resulted in enhanced apoptosis even in CLL cells cultured under conditions that simulate the tumor microenvironment. These data provide a mechanistic rationale for testing the combination of duvelisib and venetoclax in the clinic. Such combination regimen (NCT02640833) is being evaluated for patients with B-cell malignancies including CLL.

Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.

PubMed

Saydam, Guray; Haznedaroglu, Ibrahim C; Kaynar, Leylagul; Yavuz, Akif S; Ali, Ridvan; Guvenc, Birol; Akay, Olga M; Baslar, Zafer; Ozbek, Ugur; Sonmez, Mehmet; Aydin, Demet; Pehlivan, Mustafa; Undar, Bulent; Dagdas, Simten; Ayyildiz, Orhan; Akkaynak, Diyar Z; Akin, Gulnur; İlhan, Osman

2018-02-27

Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1 IS ]) by 12 months. Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. This study is registered with ClinicalTrials.gov (NCT01274351). Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR 4.5 (BCR-ABL1 IS ≤0.0032%) by 12 months. During the first year of treatment, one patient progressed to blast crisis and two patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP with low and intermediate risk.

A prospective study of primary care patients with musculoskeletal pain: the identification of predictive factors for chronicity.

PubMed Central

Potter, R G; Jones, J M; Boardman, A P

2000-01-01

Primary care faces the challenge of reducing the proportion of patients continuing with musculoskeletal pain beyond the acute phase. This study assessed patients presenting in general practice with a four- to 12-week history of pain and re-assessed them 12 weeks later. Patients whose pain was described as 'none' or 'slight' were allocated to the 'acute group', and those whose pain continued to be 'moderate' or 'severe' were allocated to the 'chronic group'. Comparative analysis of the two groups' responses at initial assessment identified pain intensity, active coping score, and previous pain episode to be factors independently predictive of chronicity. PMID:10750237

How Stable Is Coping in Patients with Neuropsychiatric Symptoms after Acquired Brain Injury? Changes in Coping Styles and Their Predictors in the Chronic Phase.

PubMed

Wolters Gregório, Gisela; Ponds, Rudolf W H M; Smeets, Sanne M J; Jonker, Frank; Pouwels, Climmy G J G; van Heugten, Caroline M

2016-04-01

The objective of the study was to examine changes in coping and their predictors in patients in the chronic phase after an acquired brain injury with prominent neuropsychiatric symptoms. Patients with brain injury were recruited from consecutive admissions to the outpatient clinics of four mental health centers in the Netherlands. Patients received psychoeducation and/or one or more individual treatment sessions that were not targeting coping styles. Forty-two patients and thirty-two significant others participated. Patients reported a significantly greater use of passive and avoidance coping than both the general population and patients with brain injury without neuropsychiatric symptoms. There were statistically significant increases in avoidance coping between T1 and T2 (t = 2.0; p < 0.05). Less neuropsychiatric symptoms at T1 were associated with increases in avoidance coping, and more neuropsychiatric symptoms were associated with decreases in avoidance coping (β = -3.3; p < 0.001). Patients' underestimation of their deficits at T1 was associated with greater increases in active coping (β = -2.33; p < 0.05) than were patients' accurate estimation and overestimation of deficits at T1. Self-reported executive functioning at T1 was not associated with changes in coping. In conclusion, avoidance coping increased in the chronic phase after brain injury. The changes in coping could partially be explained by the level of neuropsychiatric symptoms and the level of self-awareness but not by self-reported executive functioning, which should be considered in treatment programs.

Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

PubMed

Hittelman, W N; Broussard, L C; McCredie, K

1979-11-01

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

[Community acquired bacterial pneumonia and comorbidity in elderly patients].

PubMed

Fatenkov, O V; Kuzmina, T M; Rubanenko, O A; Svetlova, G N; Djubailo, A V

2017-01-01

We analyzed the clinical course of pneumonia in 67 elderly patients (39 females and 28 males, mean age 74,4±5,2 years) with chronic heart failure and chronic obstructive pulmonary disease (COPD). Patients were divided into 2 groups: 1st group - patients with COPD, 2nd group - patients without COPD. Pharmacological treatment was performed according to temperature, oxygen saturation, acute phase proteins and included ampicillin and sulbactam. The normalization of temperature and oxygen saturation was observed on 3-4 day in patients of the 1st group and on 2 day in patients of the 2nd group, normalization of leukocyte count and erythrocyte sedimentation rate - on 12-13 and 7-8 days, acute phase indicators (C-reactive protein, fibrinogen) on 7 and 5 days, correspondingly. Positive dynamics of chest X-ray was observed on 13 day in patients of the 1st group (the second control and the replacement of antibiotic for levofloxacin) and on 8 day in patients of the 2nd group (the first control).

Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study.

PubMed

Ross, David M; Masszi, Tamas; Gómez Casares, María Teresa; Hellmann, Andrzej; Stentoft, Jesper; Conneally, Eibhlin; Garcia-Gutierrez, Valentin; Gattermann, Norbert; le Coutre, Philipp D; Martino, Bruno; Saussele, Susanne; Giles, Francis J; Radich, Jerald P; Saglio, Giuseppe; Deng, Weiping; Krunic, Nancy; Bédoucha, Véronique; Gopalakrishna, Prashanth; Hochhaus, Andreas

2018-05-01

ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis. Attempting TFR required ≥ 3 years of nilotinib, a molecular response of MR 4.5 [BCR-ABL1 ≤ 0.0032% on the International Scale (BCR-ABL1 IS )], and sustained deep molecular response (DMR) during a 1-year consolidation phase. Patients restarted nilotinib following loss of major molecular response (MMR; BCR-ABL1 IS  ≤ 0.1%). Ninety-six weeks after stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of MMR, 87 regained MMR and 81 regained MR 4.5 by the data cut-off. Ninety-six-week TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high Sokal risk scores at diagnosis, respectively. Patients consistently in MR 4.5 during consolidation had higher TFR rates (50.6%) than patients with ≥ 1 assessment without MR 4.5 during consolidation (35.0%). In a landmark analysis, 96-week TFR rates for patients with MR 4.5 , MR 4 (BCR-ABL1 IS  ≤ 0.01%) but not MR 4.5 , and MMR but not MR 4 at TFR week 12 were 82.6, 23.1, and 0%, respectively. There were no reports of disease progression or death due to CML; overall adverse event frequency decreased following TFR. Within the follow-up period, TFR did not adversely affect disease outcomes. These results demonstrate the feasibility and durability of TFR following frontline nilotinib and emphasize the importance of sustained DMR for TFR.

The role of the cervical spine in post-concussion syndrome.

PubMed

Marshall, Cameron M; Vernon, Howard; Leddy, John J; Baldwin, Bradley A

2015-07-01

While much is known regarding the pathophysiology surrounding concussion injuries in the acute phase, there is little evidence to support many of the theorized etiologies to post-concussion syndrome (PCS); the chronic phase of concussion occurring in ∼ 10-15% of concussed patients. This paper reviews the existing literature surrounding the numerous proposed theories of PCS and introduces another potential, and very treatable, cause of this chronic condition; cervical spine dysfunction due to concomitant whiplash-type injury. We also discuss a short case-series of five patients with diagnosed PCS having very favorable outcomes following various treatment and rehabilitative techniques aimed at restoring cervical spine function.

Bilineal Extramedullary Blast Crisis as an Initial Presentation of Chronic Myeloid Leukemia: A Case Report and Literature Review

PubMed Central

Gao, Xiaoning; Li, Jie; Wang, Lili; Lin, Ji; Jin, Hongshi; Xu, Yihan; Wang, Nan; Zhao, Yu; Liu, Daihong; Yu, Li; Wang, Quanshun

2016-01-01

Patient: Male, 49 Final Diagnosis: T-lymphoid/myeloid bilineal blastic transformation of CML Symptoms: Rapidly enlarging mass in left neck Medication: — Clinical Procedure: Biopsy of the left submandibular lymph nodes Specialty: Hematology Objective: Rare co-existance of disease or pathology Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia chromosome generated by the reciprocal translocation t(9: 22)(q34;q11). CML is usually diagnosed in the chronic phase. Blast crisis represents an advanced phase of CML. Extramedullary blast crisis as the initial presentation of CML with bone marrow remaining in chronic phase is an unusual event. Further, extramedullary blast crisis with T lymphoid/myeloid bilineal phenotype as an initial presentation for CML is extremely unusual. Case Report: Here, we report the case of a 49-year-old male with rapidly enlarged submandibular lymph nodes. Biopsy specimen from the nodes revealed a characteristic appearance with morphologically and immunohistochemically distinct myeloblasts and T lymphoblasts co-localized in 2 adjacent regions, accompanied by chronic phase of the disease in bone marrow. The presence of the BCR/ABL1 fusion gene within both cellular populations in this case confirmed the extramedullary disease represented a localized T lymphoid/myeloid bilineal blastic transformation of CML. After 3 courses of combined chemotherapy plus tyrosine kinase inhibitor treatment, the mass was completely regressed with a 3-log decrease in BCR/ABL1 transcript from baseline. Five months after the diagnosis, the patient showed diminished vision, hand tremors, and weakness of lower extremities. Flow cytometric immunophenotyping of cerebrospinal fluid revealed the presence of myeloid blasts. An isolated central nervous system relapse of leukemia was identified. Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. Conclusions: The possibility of extramedullary blast crisis as an initial presentation in patients with CML should be considered. Further, an isolated central nervous system blast crisis should be considered if neurological symptoms evolve in patients who have shown a good response to therapy. PMID:27784881

BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

ClinicalTrials.gov

2013-01-22

Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era - a report from the Swedish CML register.

PubMed

Söderlund, Stina; Dahlén, Torsten; Sandin, Fredrik; Olsson-Strömberg, Ulla; Creignou, Maria; Dreimane, Arta; Lübking, Anna; Markevärn, Berit; Själander, Anders; Wadenvik, Hans; Stenke, Leif; Richter, Johan; Höglund, Martin

2017-01-01

The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment. Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment. The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively. In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia.

PubMed

Radich, Jerald P; Mauro, Michael J

2017-08-01

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors has led to a reduction in mortalities. Thus, the estimated prevalence of CML is increasing. The National Comprehensive Cancer Network and the European Leukemia Net guidelines incorporate frequent molecular monitoring of the fusion BCR-ABL transcript to ensure that patients reach and keep treatment milestones. Most patients with CML are diagnosed in the chronic phase, and approximately 10% to 30% of these patients will at some time in their course meet definition criteria of resistance to imatinib. Copyright © 2017 Elsevier Inc. All rights reserved.

Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

ClinicalTrials.gov

2018-04-20

Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

The Efficacy of Reduced-dose Dasatinib as a Subsequent Therapy in Patients with Chronic Myeloid Leukemia in the Chronic Phase: The LD-CML Study of the Kanto CML Study Group

PubMed Central

Iriyama, Noriyoshi; Ohashi, Kazuteru; Hashino, Satoshi; Kimura, Shinya; Nakaseko, Chiaki; Takano, Hina; Hino, Masayuki; Uchiyama, Michihiro; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

2017-01-01

Objective The aim of this study was to prospectively investigate the efficacy and safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were being treated with low-dose imatinib (≤200 mg/day), but were resistant to this agent were enrolled in the current study (referred to as the LD-CML study). Results There subjects included 9 patients (4 men and 5 women); all were treated with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not experienced major molecular response (MMR; BCR-ABL1 transcript ≤0.1% according to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS ≤0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by cytotoxic lymphocyte predominance. There was no mortality or disease progression, and all continue to receive dasatinib therapy at 18 months with only 2 patients requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR and DMR without severe toxicity in patients with CML-CP who are unable to achieve MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be considered for patients in this setting, especially if they are otherwise considering a cessation of treatment. PMID:29033428

Clinical relevance of the breakpoint sites within the M-BCR in 50 patients from Argentina with chronic myeloid leukemia.

PubMed

Giere, I A; Larripa, I B

1996-08-01

Fifty patients from Argentina with chronic myeloid leukemia (CML) were studied in order to characterize the breakpoint site within the major breakpoint cluster region (M-BCR) and its relationship with the duration of the chronic phase (CP). The DNA digestion with the restriction enzymes: Bgl II, BAM HI and Hind III and hybridization with the 1.2Kb Hind III-Bgl II bcr probe showed that 56% of cases had the breakpoint in 5'M-bcr region and the remaining 44% in 3'M-bcr region. The duration of chronic phase from diagnosis to the onset of the blast crisis (BC) was correlated with the location of the breakpoint within the M-bcr and no statistical differences were observed between the 5' and the 3' groups. These data indicate that the breakpoint site within the bcr gene is not a prognostic indicator of the duration of CP of the disease.

'Real-life' study of imatinib therapy in chronic phase-chronic myeloid leukemia: A novel retrospective observational longitudinal analysis.

PubMed

Merante, Serena; Ferretti, Virginia; Elena, Chiara; Calvello, Celeste; Rocca, Barbara; Zappatore, Rita; Cavigliano, Paola; Orlandi, Ester

2017-01-01

Imatinib is a cornerstone of treatment of chronic myeloid leukemia. It remains unclear whether transient treatment discontinuation or dose changes affect outcome and this approach has not yet been approved for use outside clinical trials. We conducted a retrospective single-institution observational study to evaluate factors affecting response in 'real-life' clinical practice in 138 chronic myeloid leukemia patients in chronic phase treated with imatinib. We used a novel longitudinal data analytical model, with a generalized estimating equation model, to study BCR-ABL variation according to continuous standard dose, change in dose or discontinuation; BCR-ABL transcript levels were recorded. Treatment history was subdivided into time periods for which treatment was given at constant dosage (total 483 time periods). Molecular and cytogenetic complete response was observed after 154 (32%) and 358 (74%) time periods, respectively. After adjusting for length of time period, no association between dose and cytogenetic complete response rate was observed. There was a significantly lower molecular complete response rate after time periods at a high imatinib dosage. This statistical approach can identify individual patient variation in longitudinal data collected over time and suggests that changes in dose or discontinuation of therapy could be considered in patients with appropriate biological characteristics.

[Management of patients with simple cervical distortions].

PubMed

Foletti, G; Regli, F

1995-11-11

Common distortion of the cervical spine without evidence of neurological or osteoligamentary damage is a frequent consequence of indirect head and neck trauma. The mechanism of the injury (called "whiplash", "coup de lapin", or "Schleudertrauma") does not imply direct trauma to the head or neck. In the acute phase, common distortion of the cervical spine requires treatment. Rapid management may avoid or considerably reduce the chronic pain syndrome with the characteristic chronic tension-like headache. The chronic pain and the numerous associated functional disorders are not well understood: certain factors favour central and peripheral dysfunction and others emphasize the importance of extra-trauma phenomena. In our opinion, extra-trauma phenomena would explain the invalidating nature of pain in a small number of patients. Management of these chronic patients requires a multidisciplinary approach aimed at helping the patient overcome the inconveniences of this condition.

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial

PubMed Central

O’Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

2014-01-01

Summary Background Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. Methods In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Findings Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65–84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1–2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one developed grade 4 thrombocytopenia. After a median follow-up of 22·1 months (IQR 18·4–23·2), 22 (71%) of 31 patients achieved an objective response (95% CI 52·0–85·8); four patients (13%) had a complete response, one patient (3%) had a nodular partial response, and 17 (55%) patients had a partial response. Interpretation The safety and activity of ibrutinib in elderly, previously untreated patients with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is encouraging, and merits further investigation in phase 3 trials. Funding Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD. PMID:24332241

Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial.

PubMed

Lipton, Jeffrey H; Chuah, Charles; Guerci-Bresler, Agnès; Rosti, Gianantonio; Simpson, David; Assouline, Sarit; Etienne, Gabriel; Nicolini, Franck E; le Coutre, Philipp; Clark, Richard E; Stenke, Leif; Andorsky, David; Oehler, Vivian; Lustgarten, Stephanie; Rivera, Victor M; Clackson, Timothy; Haluska, Frank G; Baccarani, Michele; Cortes, Jorge E; Guilhot, François; Hochhaus, Andreas; Hughes, Timothy; Kantarjian, Hagop M; Shah, Neil P; Talpaz, Moshe; Deininger, Michael W

2016-05-01

Ponatinib has shown potent activity against chronic myeloid leukaemia that is resistant to available treatment, although it is associated with arterial occlusion. We investigated whether this activity and safety profile would result in superior outcomes compared with imatinib in previously untreated patients with chronic myeloid leukaemia. The Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC) study was a randomised, open-label, phase 3 trial designed to assess the efficacy and safety of ponatinib, compared with imatinib, in newly diagnosed patients with chronic-phase chronic myeloid leukaemia. Patients from 106 centres in 21 countries were randomly assigned (1:1, with stratification by Sokal score at diagnosis) using an interactive voice and web response system to receive oral ponatinib (45 mg) or imatinib (400 mg) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met. Eligible patients were at least 18 years of age, within 6 months of diagnosis, and Philadelphia chromosome-positive by cytogenetic assessment, with Eastern Cooperative Oncology Group performance status of 0-2, and had not previously been treated with tyrosine kinase inhibitors. The primary endpoint was major molecular response at 12 months. Patients who remained on study and had molecular assessments at specified timepoints were studied at those timepoints. Safety analyses included all treated patients, as per study protocol. This trial is registered with ClinicalTrials.gov, number NCT01650805. Between Aug 14, 2012, and Oct 9, 2013, 307 patients were randomly assigned to receive ponatinib (n=155) or imatinib (n=152). The trial was terminated early, on Oct 17, 2013, following concerns about vascular adverse events observed in patients given ponatinib in other trials. Trial termination limited assessment of the primary endpoint of major molecular response at 12 months, as only 13 patients in the imatinib group and ten patients in the ponatinib group could be assessed at this timepoint; the proportion of patients achieving a major molecular response at 12 months did not differ significantly between the two groups (eight [80%] of ten patients given ponatinib and five [38%] of 13 patients given imatinib; p=0·074). 11 (7%) of 154 patients given ponatinib and three (2%) of 152 patients given imatinib had arterial occlusive events (p=0·052); arterial occlusive events were designated serious in ten (6%) of 154 patients given ponatinib and in one (1%) of 152 patients given imatinib (p=0·010). The data monitoring committee criterion for risk assessment (significant difference in serious grade 3 or 4 ischaemic events between groups) was not met (five [3%] of 154 vs one [1%] of 152; p=0·21). Grade 3 or 4 adverse events observed in more than 5% of patients in the ponatinib group were increased lipase (22 [14%] of 154 vs three [2%] of 152 with imatinib), thrombocytopenia (19 [12%] of 154 vs ten [7%] of 152 with imatinib), rash (ten [6%] of 154 vs two [1%] of 152 with imatinib). In the imatinib group, grade 3 or 4 adverse events observed in more than 5% of patients were neutropenia (12 [8%] of 152 vs five [3%] of 154 with ponatinib) and thrombocytopenia (ten [7%] of 152 vs 19 [12%] of 154 with ponatinib). Serious adverse events that occurred in three or more patients given ponatinib were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). No serious adverse event occurred in three or more patients given imatinib. The efficacy of ponatinib treatment of newly diagnosed chronic-phase chronic myeloid leukaemia compared with imatinib could not be assessed due to trial termination, but preliminary data suggest there might be benefit, although with more arterial occlusive events than with imatinib at the doses studied. Because the EPIC trial was terminated early, efficacy of ponatinib in this setting remains to be established. ARIAD Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd.

PubMed

Hughes, Timothy P; Munhoz, Eduardo; Aurelio Salvino, Marco; Ong, Tee Chuan; Elhaddad, Alaa; Shortt, Jake; Quach, Hang; Pavlovsky, Carolina; Louw, Vernon J; Shih, Lee-Yung; Turkina, Anna G; Meillon, Luis; Jin, Yu; Acharya, Sandip; Dalal, Darshan; Lipton, Jeffrey H

2017-10-01

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188). © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

ClinicalTrials.gov

2014-04-28

Accelerated Phase Chronic Myelogenous Leukemia; Acute Leukemias of Ambiguous Lineage; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Acute Undifferentiated Leukemia; Aggressive NK-cell Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Noncutaneous Extranodal Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity, phase 3

NASA Technical Reports Server (NTRS)

Rubin, A. L.; Stenzel, K. H.; Cheigh, J. S.; Seaman, G. V. F.; Novogrodsky, A.

1977-01-01

Electrophoretic mobilities (EPM) of peripheral lymphocytes were studied from normal subjects, chronic hemodialysis patients and kidney transplant recipients. A technique to separate B lymphocytes and null cells from non-T lymphocyte preparation was developed. The experiments were designed to determine which subpopulation of the non-T lymphocytes is primarily affected and shows a decreased EPM in chronic hemodialysis patients and kidney transplant recipients.

RN Diabetes Virtual Case Management: A New Model for Providing Chronic Care Management.

PubMed

Brown, Nancy N; Carrara, Barbara E; Watts, Sharon A; Lucatorto, Michelle A

2016-01-01

The U.S. chronic disease health care system has substantial gaps in delivery of services. New models of care change traditional delivery of care and explore new settings for care. This article describes a new model of diabetes chronic care delivery: nurse-delivered care that includes protocol-based insulin titration and patient education delivered solely in a virtual environment. In phase 1, the clinical outcome of time to achievement of glycated hemoglobin (A(1C)) goals (P < .001; 95% confidence interval, 1.68-2.24) was significantly improved by registered nurse (RN) standing order intervention (n = 24) as compared with historical controls (n = 28). In phase 2, patients who were referred to an RN-managed insulin titration protocol with individualized A(1C) goals had a significant (P < .001; 95% confidence interval, 1.680-2.242) reduction in results from a mean of 9.6% at baseline to 7.7% at completion. Average patient age was 66 years, with a mean duration of 11 years diagnosed with diabetes. Safety was demonstrated by the absence of hypoglycemia related to RN protocol adjustment. There were no admissions or emergency room (ER) visits for hypoglycemia. This study demonstrates safety and efficacy of RN virtual chronic disease management for an older population of patients with long-standing diabetes.

Tapering off long-term opioid therapy in chronic non-cancer pain patients: a randomized clinical trial.

PubMed

Kurita, Geana Paula; Højsted, Jette; Sjøgren, Per

2018-05-13

The indications for initiating long-term opioid treatment (L-TOT) for chronic non-cancer pain (CNCP) are often unclear and associated with problematic use. This study aimed at evaluating the efficacy of stabilizing opioid therapy followed by a sequential opioid tapering off program in CNCP patients. A randomized clinical trial with a medications stabilization period (Phase 1) followed by a opioid tapering off program (Phase 2). In Phase 2, patients were randomized to Control Group (stable treatment) or Taper off Group (sequential opioid dose reduction) and assessed at baseline, after stabilization and up to six months. Primary outcomes: measures of cognitive function; secondary outcomes: pain, sleep, rest, quality of life, depression, anxiety, opioid misuse, and opioid withdrawal symptoms. Two hundred seventy-four patients were screened; 75 were included, out of which 40 dropped out before Phase 2. Those who succeeded Phase 1 (n=35) had weak/moderate improvements of psychomotor function (p=0.020), sleeping hours (p=0.031), opioid withdrawal symptoms (p=0.019), measures of quality of life (p≤0.043) and opioid misuse scores (p=0.003). In Phase 2, patients in Taper off Group (n=15) experienced stable pain intensity and felt significantly more rested at third assessment than the Control Group (n=20). The opioid tapering off program was not successful due to the vast number of dropouts. Phase 1 was associated with weak to moderate improvements on psychomotor function, sleeping, opioid withdrawal symptoms, quality of life, and reduced risk of opioid misuse. In the intervention group of Phase 2, pain intensity was stable and patients felt more rested. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test.

PubMed

Orbe, Josune; Zudaire, Maite; Serrano, Rosario; Coma-Canella, Isabel; Martínez de Sizarrondo, Sara; Rodríguez, Jose A; Páramo, Jose A

2008-02-01

Atherosclerosis is the most common pathophysiologic substrate of coronary artery disease (CAD). Whereas plaque progression and arterial remodeling are critical components in chronic CAD, intracoronary thrombosis over plaque disruption is causally related to acute CAD. It was the objective of this study to investigate the differences between prior acute CAD and chronic CAD by a simple global coagulation assay measuring thrombin generation. A cross-sectional study involving 15 healthy controls, 35 patients with chronic stable CAD, and 60 patients after an episode of acute myocardial infarction (AMI) was performed. Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). In each patient the lag phase, velocity index and peak thrombin were obtained from the thrombogram profile. Traditional cardiovascular risk factors were recorded, and the inflammatory markers, fibrinogen and hs-C-reactive protein were determined. Compared with stable CAD patients, showing normal thrombograms, those with previous AMI showed earlier lag phase (p < 0.05) and significant increase of both the velocity index (p < 0.001) and peak thrombin (p < 0.05), indicating faster and higher thrombin generation in the AMI group. Differences in thrombin generation between stable and acute CAD patients remained significant (p < 0.001) after adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia). In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value to monitor hypercoagulable/vulnerable blood and/or guide therapy in CAD.

The European medicines agency review of bosutinib for the treatment of adult patients with chronic myelogenous leukemia: summary of the scientific assessment of the committee for medicinal products for human use.

PubMed

Hanaizi, Zahra; Unkrig, Christoph; Enzmann, Harald; Camarero, Jorge; Sancho-Lopez, Arantxa; Salmonson, Tomas; Gisselbrecht, Christian; Laane, Edward; Pignatti, Francesco

2014-04-01

On March 27, 2013, a conditional marketing authorization valid throughout the European Union was issued for bosutinib (Bosulif) for the treatment of adult patients with chronic-phase, accelerated-phase, and blast-phase Philadelphia chromosome positive (Ph⁺) chronic myelogenous leukemia (CML) previously treated with one tyrosine kinase inhibitor or more and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options. Bosutinib is a kinase inhibitor that targets the BCR-ABL kinase. The recommended dose is 500 mg of bosutinib once daily. The main evidence of efficacy for bosutinib was based on a CML subgroup analysis of study 3160A4-200, a phase I/II study of bosutinib in Ph⁺ leukemia in imatinib-resistant or intolerant CML. The subgroup was defined based on the presence of a BCR-ABL kinase domain mutation that would be expected to confer resistance to dasatinib (F317, E255) or nilotinib (E255, Y253, F359) and expected to have sensitivity to bosutinib or based on the presence of medical conditions or prior toxicities that may predispose the patient to unacceptable risk in the setting of nilotinib or dasatinib therapy. A conditional marketing authorization was granted because of the limited evidence of efficacy and safety currently supporting this last-line indication.

NeutroPhase® in chronic non-healing wounds

PubMed Central

Crew, John; Varilla, Randell; Rocas, Thomas Allandale; Debabov, Dmitri; Wang, Lu; Najafi, Azar; Rani, Suriani Abdul; Najafi, Ramin (Ron); Anderson, Mark

2012-01-01

Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient’s morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase® as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase® is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase® with and without NPWT. NeutroPhase® was non-toxic to living tissues. PMID:23272294

Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.

PubMed

Christoph, Annette; Eerdekens, Marie-Henriette; Kok, Maurits; Volkers, Gisela; Freynhagen, Rainer

2017-09-01

Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 μg once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.

Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

ClinicalTrials.gov

2017-02-13

Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity.

PubMed

Schiffer, Charles A; Cortes, Jorge E; Hochhaus, Andreas; Saglio, Giuseppe; le Coutre, Philipp; Porkka, Kimmo; Mustjoki, Satu; Mohamed, Hesham; Shah, Neil P

2016-05-01

The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed. Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398-1407. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.

PubMed

Sorge, Jürgen; Sittl, Reinhard

2004-11-01

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex distribution, age, height, and body weight Patients receiving buprenorphine TES significantly reduced their consumption of buprenorphine SL tablets in the double-blind phase compared with patients receiving placebo (reduction of 0.6 [0.4] mg vs 0.4 [0.4] mg; P = 0.03). The relationship between the buprenorphine SL dose in the run-in phase and the number of buprenorphine SL tablets required in the double-blind phase was dose dependent in the active-treatment group only. Patients' assessments of pain intensity and pain relief suggested better analgesia with buprenorphine TES than with placebo, although the differences did not reach statistical significance. The proportion of patients who reported sleeping for >6 hours uninterrupted by pain in the double-blind phase compared with the run-in phase increased by 6.4% in the buprenorphine TDS group (35.6% vs 292%, respectively), compared with a decrease of 5.9% in the placebo group (40.4% vs 463%); no statistical analysis of sleep duration data was performed. Buprenorphine TDS was well tolerated, with adverse events generally similar to those associated with other opioids. The incidence of systemic adverse events in the double-blind phase was similar in the 2 treatment groups (28.9% buprenorphine TDS, 27.6% placebo), with the most common adverse events being nausea, dizziness, and vomiting. After patch removal, skin reactions (mainly mild or moderate pruritus and erythema) were seen in 35.6% of the buprenorphine TDS group and 25.5% of the placebo group. In the population studied, buprenorphine TDS provided adequate pain relief, as well as improvements in pain intensity and duration of pain-free sleep. It may be considered a therapeutic option for the treatment of moderate to severe chronic pain.

Do telemonitoring projects of heart failure fit the Chronic Care Model?

PubMed Central

Willemse, Evi; Adriaenssens, Jef; Dilles, Tinne; Remmen, Roy

2014-01-01

This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner. Background The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation. Methods This qualitative study describes seven non-invasive home-care telemonitoring projects in patients with heart failure in Belgium. A qualitative design, including interviews and literature review, was used to describe the correspondence of these home-care telemonitoring projects with the dimensions of the Chronic Care Model. Results The projects were situated in primary and secondary health care. Their primary goal was to reduce the number of readmissions for chronic heart failure. None of these projects succeeded in a final implementation of telemonitoring in home care after the pilot phase. Not all the projects were initiated to accomplish all of the dimensions of the Chronic Care Model. A central role for the patient was sparse. Conclusion Limited financial resources hampered continuation after the pilot phase. Cooperation and coordination in telemonitoring appears to be major barriers but are, within primary care as well as between the lines of care, important links in follow-up. This discrepancy can be prohibitive for deployment of good chronic care. Chronic Care Model is recommended as basis for future. PMID:25114664

Do telemonitoring projects of heart failure fit the Chronic Care Model?

PubMed

Willemse, Evi; Adriaenssens, Jef; Dilles, Tinne; Remmen, Roy

2014-07-01

This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner. The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation. This qualitative study describes seven non-invasive home-care telemonitoring projects in patients with heart failure in Belgium. A qualitative design, including interviews and literature review, was used to describe the correspondence of these home-care telemonitoring projects with the dimensions of the Chronic Care Model. The projects were situated in primary and secondary health care. Their primary goal was to reduce the number of readmissions for chronic heart failure. None of these projects succeeded in a final implementation of telemonitoring in home care after the pilot phase. Not all the projects were initiated to accomplish all of the dimensions of the Chronic Care Model. A central role for the patient was sparse. Limited financial resources hampered continuation after the pilot phase. Cooperation and coordination in telemonitoring appears to be major barriers but are, within primary care as well as between the lines of care, important links in follow-up. This discrepancy can be prohibitive for deployment of good chronic care. Chronic Care Model is recommended as basis for future.

Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2017-04-07

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Aggressive Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

Six months of daily treatment with vardenafil improves parameters of endothelial inflammation and of hypogonadism in male patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, prospective trial.

PubMed

Santi, Daniele; Granata, Antonio R M; Guidi, Alessandro; Pignatti, Elisa; Trenti, Tommaso; Roli, Laura; Bozic, Roberto; Zaza, Stefano; Pacchioni, Chiara; Romano, Stefania; Nofer, Jerzy Roch; Rochira, Vincenzo; Carani, Cesare; Simoni, Manuela

2016-04-01

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men. A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted. In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10  mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry). IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects. This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism in diabetic, hypogonadal men. © 2016 European Society of Endocrinology.

Difference in the craniocaudal gradient of the maximum pixel value change rate between chronic obstructive pulmonary disease patients and normal subjects using sub-mGy dynamic chest radiography with a flat panel detector system.

PubMed

Yamada, Yoshitake; Ueyama, Masako; Abe, Takehiko; Araki, Tetsuro; Abe, Takayuki; Nishino, Mizuki; Jinzaki, Masahiro; Hatabu, Hiroto; Kudoh, Shoji

2017-07-01

To compare the craniocaudal gradients of the maximum pixel value change rate (MPCR) during tidal breathing between chronic obstructive pulmonary disease (COPD) patients and normal subjects using dynamic chest radiography. This prospective study was approved by the institutional review board and all participants provided written informed consent. Forty-three COPD patients (mean age, 71.6±8.7 years) and 47 normal subjects (non-smoker healthy volunteers) (mean age, 54.8±9.8 years) underwent sequential chest radiographs during tidal breathing in a standing position using dynamic chest radiography with a flat panel detector system. We evaluated the craniocaudal gradient of MPCR. The results were analyzed using an unpaired t-test and the Tukey-Kramer method. The craniocaudal gradients of MPCR in COPD patients were significantly lower than those in normal subjects (right inspiratory phase, 75.5±48.1 vs. 108.9±42.0s -1 cm -1 , P<0.001; right expiratory phase, 66.4±40.6 vs. 89.8±31.6s -1 cm -1 , P=0.003; left inspiratory phase, 75.5±48.2 vs. 108.2±47.2s -1 cm -1 , P=0.002; left expiratory phase, 60.9±38.2 vs. 84.3±29.5s -1 cm -1 , P=0.002). No significant differences in height, weight, or BMI were observed between COPD and normal groups. In the sub-analysis, the gradients in severe COPD patients (global initiative for chronic obstructive lung disease [GOLD] 3 or 4, n=26) were significantly lower than those in mild COPD patients (GOLD 1 or 2, n=17) for both right and left inspiratory/expiratory phases (all P≤0.005). A decrease of the craniocaudal gradient of MPCR was observed in COPD patients. The craniocaudal gradient was lower in severe COPD patients than in mild COPD patients. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies

ClinicalTrials.gov

2017-04-05

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

Motor and cognitive performances of parkinsonian patients in the on and off phases of the disease.

PubMed Central

Girotti, F; Carella, F; Grassi, M P; Soliveri, P; Marano, R; Caraceni, T

1986-01-01

Twenty-one Parkinsonian patients were tested in on and off phases during chronic levodopa therapy for cognitive function, affective status, and evaluation of motor performance with reaction and movement times. A worsening of mood was observed from the on to the off phase. No variation in cognitive performance was observed from the on to the off phase in spite of evident motor changes. Mood changes during on-off variations may reflect involvement of mesocortical and mesolimbic dopaminergic systems. PMID:3734822

Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience.

PubMed

Giona, Fiorina; Putti, Maria C; Micalizzi, Concetta; Menna, Giuseppe; Moleti, Maria L; Santoro, Nicola; Iaria, Grazia; Ladogana, Saverio; Burnelli, Roberta; Consarino, Caterina; Varotto, Stefania; Tucci, Francesca; Messina, Chiara; Nanni, Mauro; Diverio, Daniela; Biondi, Andrea; Pession, Andrea; Locatelli, Franco; Piciocchi, Alfonso; Gottardi, Enrico; Saglio, Giuseppe; Foà, Robin

2015-08-01

Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91.5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0.1% (major molecular response; MMR) and ≤0.01% (molecular response; MR) at 12 months were 66.6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78.6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML. © 2015 John Wiley & Sons Ltd.

Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy.

PubMed

Miyamura, Koichi; Miyamoto, Toshihiro; Tanimoto, Mitsune; Yamamoto, Kazuhito; Kimura, Shinya; Kawaguchi, Tatsuya; Matsumura, Itaru; Hata, Tomoko; Tsurumi, Hisashi; Saito, Shigeki; Hino, Masayuki; Tadokoro, Seiji; Meguro, Kuniaki; Hyodo, Hideo; Yamamoto, Masahide; Kubo, Kohmei; Tsukada, Junichi; Kondo, Midori; Aoki, Makoto; Okada, Hikaru; Yanada, Masamitsu; Ohyashiki, Kazuma; Taniwaki, Masafumi

2016-12-01

Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874. Copyright © 2016 Elsevier Ltd. All rights reserved.

A propensity score matching analysis of dasatinib and nilotinib as a frontline therapy for patients with chronic myeloid leukemia in chronic phase.

PubMed

Takahashi, Koichi; Kantarjian, Hagop M; Yang, Yulong; Sasaki, Koji; Jain, Preetesh; DellaSala, Sara; Ravandi, Farhad; Kadia, Tapan; Pemmaraju, Naveen; Daver, Naval; Borthakur, Gautam; Garcia-Manero, Guillermo; Jabbour, Elias; Cortes, Jorge E

2016-11-15

Both dasatinib and nilotinib are approved frontline therapy for chronic myeloid leukemia in chronic phase (CML-CP) based on randomized trials compared with imatinib. However, no head-to-head comparison of dasatinib and nilotinib has been conducted in patients with newly diagnosed CML-CP. The authors conducted a propensity score (PS) matched comparison of patients with CML-CP who received frontline therapy with either dasatinib (N = 102) or nilotinib (N = 104) under the respective phase 2 trials conducted in parallel. PS matching resulted in 87 patients from each trial being matched for pretreatment characteristics. The 3-month BCR-ABL1/ABL1 ratio <10% rate was 93% with dasatinib and 94% with nilotinib (P = .25); the rates of major molecular response at 12 months were 77% and 85%, respectively (P = .13); and the rates of molecular response with 4.5-log reduction in the ratio at 36 months were 66% and 64%, respectively (P = .96). All other clinically relevant responses were similar between the 2 treatment cohorts. The 3-year probability of event-free survival was 89% among the patients who received dasatinib and 87% among those who received nilotinib (P = .99), and the corresponding 3-year overall survival probabilities were 99% and 93%, respectively (P = .95). No statistical difference was observed between the dasatinib and nilotinib groups in any of the other survival endpoints. The treatment discontinuation rate also was similar between the 2 cohorts (dasatinib group, 18%; nilotinib group, 19%; P = .82). In a PS-matched cohort of patients with newly diagnosed CML-CP, dasatinib and nilotinib offer similar response and survival outcomes. Both drugs can be considered reasonable standard-of-care options as first-line therapy for patients with CML-CP. Cancer 2016;122:3336-3343. © 2016 American Cancer Society. © 2016 American Cancer Society.

Imatinib Intolerance Is Associated With Blastic Phase Development in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia.

PubMed

Ángeles-Velázquez, Jorge Luis; Hurtado-Monroy, Rafael; Vargas-Viveros, Pablo; Carrillo-Muñoz, Silvia; Candelaria-Hernández, Myrna

2016-08-01

Over the past years, the survival of patients with Philadelphia-positive chronic myeloid leukemia (CML Ph(+)) has increased as a result of therapy with tyrosin kinase inhibitors (TKIs). Intolerance to TKIs has been described in approximately 20% of patients receiving treatment. We studied the incidence of imatinib intolerance in patients with CML Ph(+) and their outcome in our CML reference site, as there is no information about the evolution of patients intolerant to TKIs. A group of 86 patients with CML Ph(+) receiving imatinib monotherapy who abandoned treatment were the basis for this study. We present the trends of their disease evolution. The median of age at diagnosis was 42 years. Within a year, 19 (22%) of 86 patients developed imatinib intolerance, all of them with grade III or IV disease that required imatinib dose reduction or discontinuation. Of these patients, 16 (84%) of 19 developed transformation to blastic phase. The cumulative incidences of blastic phase development were 47% in the nonintolerant group and 84% in the intolerant group. There was a relative risk for those with imatinib intolerance to develop blastic phase of 1.78 (95% confidence interval, 1.28 to 2.42) (P < .05). Most imatinib-intolerant patients develop blastic phase transformation, with a poor survival of 3 to 6 months; no effective rescue treatment is available. Future research should to determine whether the origin of this evolution is really due to the intolerance itself or whether it is due to a more aggressive form of the disease, perhaps related to genetic transformation. Copyright © 2016 Elsevier Inc. All rights reserved.

Deep molecular responses for treatment-free remission in chronic myeloid leukemia.

PubMed

Dulucq, Stéphanie; Mahon, Francois-Xavier

2016-09-01

Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A phase I/II trial of oxidized autologous tumor vaccines during the "watch and wait" phase of chronic lymphocytic leukemia.

PubMed

Spaner, David E; Hammond, Caitlin; Mena, Jenny; Foden, Cindy; Deabreu, Andrea

2005-07-01

Based on their activity in patients with advanced stage chronic lymphocytic leukemia (CLL), a phase I/II study was designed to evaluate the feasibility, safety, and efficacy of autologous vaccines made from oxidized tumor cells in patients with earlier stage CLL, and to determine an optimal schedule of injections. Eighteen patients (at risk for disease progression and with white blood cell counts between 15 and 100 x 10(6) cells/ml) were injected intramuscularly with 10 ml of oxidized autologous blood (composed mainly of CLL cells) either 12 times over 6 weeks (group 1), 12 times over 16 days (group 2), or 4 times over 6 weeks (group 3). Fourteen out of eighteen patients had Rai stage 0-II disease, while 4/18 had stage III-IV disease but did not require conventional treatment. Partial clinical responses, associated with enhanced anti-tumor T cell activity in vitro, were observed in 5/18 patients of whom three were in group 2. Stable disease was observed in six patients while disease progression appeared not to be affected in the remaining patients. Toxicity was minimal. Vaccination with oxidized autologous tumor cells appears worthy of further investigation and may be a potential alternative to a "watch and wait" strategy for selected CLL patients.

Validity of screening tests for Sjögren's syndrome in ambulatory patients with chronic diseases.

PubMed

Sánchez-Guerrero, Jorge; Pérez-Dosal, Marcia R; Celis-Aguilar, Erika; Cárdenas-Velázquez, Francisco; Soto-Rojas, Armando E; Avila-Casado, Carmen

2006-05-01

To determine the validity of screening tests for Sjogren's syndrome (SS) in ambulatory patients with chronic diseases. Three hundred randomly selected patients from the rheumatology and internal medicine clinics of a tertiary care center were assessed for SS according to the American-European Consensus Group criteria. During the screening phase, an interview, the European questionnaire for sicca symptoms, Schirmer-I test, and the wafer test were carried out in all patients. Patients with positive screening had confirmatory tests including fluorescein staining test, nonstimulated whole salivary flow, and autoantibody testing. Confirmatory tests were also done in 13 patients with negative screening. During the last phase, lip biopsy was proposed to patients who met preestablished criteria. Women made up 79% of the study population. Mean age of subjects was 42.8+/-15.7 years. Two hundred twenty patients (73%) had positive screening. The distribution of positive test results was: xerophthalmia 118 (39%), xerostomia 103 (34%), Schirmer-I test 101 (34%), and wafer test 187 (62%) patients. Forty (13%) patients met criteria for SS. All screening tests were useful for identifying patients with SS; however, the model composed of at least one positive response to the European questionnaire (EQ1), Schirmer-I test, and wafer test showed the best performance. Use of the European questionnaire, Schirmer-I test, and wafer test in parallel was useful for identifying patients with SS among ambulatory patients with chronic diseases.

Neuroendocrine tumor of cecum in patient treated with imatinib mesylate for blastic phase of chronic myeloid leukemia.

PubMed

Novaković, Sabina; Kovač Peić, Anamarija; Holik, Hrvoje; Coha, Božena

2017-12-01

Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of a NET as a secondary malignancy (SM) after IM treatment. SM have been described in patients on IM before. It is unclear whether these tumors are caused by imatinib or found more easily because of close follow-up.

Acute-onset chronic inflammatory demyelinating polyneuropathy: An electrodiagnostic study.

PubMed

Anadani, Mohammad; Katirji, Bashar

2015-11-01

Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an increasingly recognized CIDP subtype. Differentiating A-CIDP from Guillain-Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes. We report 3 patients with A-CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long-term treatment of these patients and review the literature on EDx studies in this syndrome. Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy. Although several features may suggest the diagnosis of A-CIDP at initial presentation, close follow-up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A-CIDP from GBS patients. © 2015 Wiley Periodicals, Inc.

MR Enterography of Inflammatory Bowel Disease with Endoscopic Correlation.

PubMed

Kaushal, Pankaj; Somwaru, Alexander S; Charabaty, Aline; Levy, Angela D

2017-01-01

Crohn disease (CD) and ulcerative colitis (UC) are the two main forms of idiopathic inflammatory bowel disease (IBD). CD is a transmural chronic inflammatory disorder that can affect any part of the gastrointestinal tract in a discontinuous distribution. UC is a mucosal and submucosal chronic inflammatory disease that typically originates in the rectum and may extend proximally in a continuous manner. In treating patients with CD and UC, clinicians rely heavily on accurate diagnoses and disease staging. Magnetic resonance (MR) enterography used in conjunction with endoscopy and histopathologic analysis can help accurately diagnose and manage disease in the majority of patients. Endoscopy is more sensitive for detection of the early-manifesting mucosal abnormalities seen with IBD and enables histopathologic sampling. MR enterography yields more insightful information about the pathologic changes seen deep to the mucosal layer of the gastrointestinal tract wall and to those portions of the small bowel that are not accessible endoscopically. CD can be classified into active inflammatory, fistulizing and perforating, fibrostenotic, and reparative and regenerative phases of disease. Although CD has a progressive course, there is no stepwise progression between these disease phases, and various phases may exist at the same time. The endoscopic and MR enterographic features of UC can be broadly divided into two categories: acute phase and subacute-chronic phase. Understanding the endoscopic features of IBD and the pathologic processes that cause the MR enterographic findings of IBD can help improve the accuracy of disease characterization and thus optimize the medication and surgical therapies for these patients. © RSNA, 2016.

Efficacy of preventive spinal manipulation for chronic low-back pain and related disabilities: a preliminary study.

PubMed

Descarreaux, Martin; Blouin, Jean-Sébastien; Drolet, Marc; Papadimitriou, Stanislas; Teasdale, Normand

2004-10-01

To document the potential role of maintenance chiropractic spinal manipulation to reduce overall pain and disability levels associated with chronic low-back conditions after an initial phase of intensive chiropractic treatments. Thirty patients with chronic nonspecific low-back pain were separated into 2 groups. The first group received 12 treatments in an intensive 1-month period but received no treatment in a subsequent 9-month period. For this group, a 4-week period preceding the initial phase of treatment was used as a control period to examine the sole effect of time on pain and disability levels. The second group received 12 treatments in an intensive 1-month period and also received maintenance spinal manipulation every 3 weeks for a 9-month follow-up period. Pain and disability levels were evaluated with a visual analog scale and a modified Oswestry questionnaire, respectively. The 1-month control period did not modify the pain and disability levels. For both groups, the pain and disability levels decreased after the intensive phase of treatments. Both groups maintained their pain scores at levels similar to the postintensive treatments throughout the follow-up period. For the disability scores, however, only the group that was given spinal manipulations during the follow-up period maintained their postintensive treatment scores. The disability scores of the other group went back to their pretreatment levels. Intensive spinal manipulation is effective for the treatment of chronic low back pain. This experiment suggests that maintenance spinal manipulations after intensive manipulative care may be beneficial to patients to maintain subjective postintensive treatment disability levels. Future studies, however, are needed to confirm the finding in a larger group of patients with chronic low-back pain.

Striving for habitual well-being in noninvasive ventilation: a grounded theory study of chronic obstructive pulmonary disease patients with acute respiratory failure.

PubMed

Sørensen, Dorthe; Frederiksen, Kirsten; Groefte, Thorbjoern; Lomborg, Kirsten

2014-06-01

To present a theoretical account of the pattern of behaviour in patients with acute respiratory failure due to chronic obstructive pulmonary disease while undergoing noninvasive ventilation in a hospital setting. Strong evidence supports a positive effect of noninvasive ventilation, but successful treatment remains a challenge. Little attention has been given to patient intolerance to noninvasive ventilation as a cause of treatment failure. A better understanding of the patients' patterns of behaviour during noninvasive ventilation may improve treatment success. A constant comparative classic grounded theory study was performed. Data collection consisted of participant observation during the treatment of 21 patients undergoing noninvasive ventilation, followed by interviews with 11 of the patients after treatment completion. Data were collected from December 2009-January 2012. A substantive theory of striving for habitual well-being was developed. The theory included three phases: initiation, transition and determination. Each phase contained a set of subcategories to indicate the dimensions of and variations in the participants' behaviour. The substantive theory revealed that the patients' behaviour was related to their breathlessness, sensation of being restrained by the mask and head gear, and the side effects of noninvasive ventilation. This inter-relationship should be addressed in the use of noninvasive ventilation for the treatment of patients with chronic obstructive pulmonary disease to achieve treatment success. © 2013 John Wiley & Sons Ltd.

Quantitation of human thymus/leukemia-associated antigen by radioimmunoassay in different forms of leukemia.

PubMed

Chechik, B E; Jason, J; Shore, A; Baker, M; Dosch, H M; Gelfand, E W

1979-12-01

Using a radioimmunoassay, increased levels of a human thymus/leukemia-associated antigen (HThy-L) have been detected in leukemic cells and plasma from most patients with E-rosette-positive acute lymphoblastic leukemia (ALL) and a number of patients with E-rosette-negative ALL, acute myeloblastic leukemia (AML), acute monomyelocytic leukemia (AMML), and acute undifferentiated leukemia (AVL). Low levels of HThy-L have been demonstrated in white cells from patients with chronic myelocytic leukemia (stable phase) and in mononuclear cells from patients with chronic lymphatic leukemia. The relationship between HThy-L and differentiation of hematopoietic cells is discussed.

Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

PubMed

Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

2013-08-01

Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.

Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: a real clinical problem?

PubMed

Iurlo, Alessandra; Orsi, Emanuela; Cattaneo, Daniele; Resi, Veronica; Bucelli, Cristina; Orofino, Nicola; Sciumè, Mariarita; Elena, Chiara; Grancini, Valeria; Consonni, Dario; Orlandi, Ester Maria; Cortelezzi, Agostino

2015-10-20

Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib. The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib). Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.

Immune Tolerant Chronic Hepatitis B: The Unrecognized Risks

PubMed Central

Kennedy, Patrick T. F.; Litwin, Samuel; Dolman, Grace E.; Bertoletti, Antonio; Mason, William S.

2017-01-01

Chronic infection with hepatitis B virus (HBV) progresses through multiple phases, including immune tolerant, immune active, immune control, and, in a subset of patients who achieve immune control, reactivation. The first, the immune tolerant phase, is considered to be prolonged in duration but essentially benign in nature, lacking long-term consequences, and thus not recommended for antiviral therapy. This review challenges the notion that the immune tolerant phase is truly benign and considers the possibility that events during this phase may contribute significantly to cirrhosis, hepatocellular carcinoma (HCC), and the premature death of 25% of HBV carriers worldwide. Thus, earlier treatment than recommended by current guidelines should be considered. Low therapeutic coverage exacerbated by restrictive treatment guidelines may facilitate disease progression in many patients but also increase the risk of neonatal and horizontal transmission from untreated mothers to their children. While a prophylactic vaccine exists, there are many areas worldwide where the treatment of adults and the delivery of an effective vaccination course to newborns present difficult challenges. PMID:28468285

CXCL9, a promising biomarker in the diagnosis of chronic Q fever.

PubMed

Jansen, Anne F M; Schoffelen, Teske; Textoris, Julien; Mege, Jean-Louis; Nabuurs-Franssen, Marrigje; Raijmakers, Ruud P H; Netea, Mihai G; Joosten, Leo A B; Bleeker-Rovers, Chantal P; van Deuren, Marcel

2017-08-09

In the aftermath of the largest Q fever outbreak in the world, diagnosing the potentially lethal complication chronic Q fever remains challenging. PCR, Coxiella burnetii IgG phase I antibodies, CRP and 18 F-FDG-PET/CT scan are used for diagnosis and monitoring in clinical practice. We aimed to identify and test biomarkers in order to improve discriminative power of the diagnostic tests and monitoring of chronic Q fever. We performed a transcriptome analysis on C. burnetii stimulated PBMCs of 4 healthy controls and 6 chronic Q fever patients and identified genes that were most differentially expressed. The gene products were determined using Luminex technology in whole blood samples stimulated with heat-killed C. burnetii and serum samples from chronic Q fever patients and control subjects. Gene expression of the chemokines CXCL9, CXCL10, CXCL11 and CCL8 was strongly up-regulated in C. burnetii stimulated PBMCs of chronic Q fever patients, in contrast to healthy controls. In whole blood cultures of chronic Q fever patients, production of all four chemokines was increased upon C. burnetii stimulation, but also healthy controls and past Q fever individuals showed increased production of CXCL9, CXCL10 and CCL8. However, CXCL9 and CXCL11 production was significantly higher for chronic Q fever patients compared to past Q fever individuals. In addition, CXCL9 serum concentrations in chronic Q fever patients were higher than in past Q fever individuals. CXCL9 protein, measured in serum or as C. burnetii stimulated production, is a promising biomarker for the diagnosis of chronic Q fever.

Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

NASA Astrophysics Data System (ADS)

Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

2016-04-01

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

Cinacalcet: AMG 073, Calcimimetics--Amgen/NPS Pharmaceuticals, KRN 1493, NPS 1493.

PubMed

2003-01-01

Cinacalcet [AMG 073, KRN 1493, NPS 1493] is an orally active, second-generation calcimimetic compound licensed by NPS Pharmaceuticals to Amgen in the US for potential treatment of hyperparathyroidism (HPT). Cinacalcet modulates (increases the sensitivity of) calcium receptors on the surface of parathyroid cells thereby inhibiting the oversecretion of parathyroid hormone, which characterises HPT. It also represents a potentially significant advance for chronic kidney disease patients diagnosed with secondary HPT, a common yet serious metabolic disorder where parathyroid hormone levels are elevated. Patients with this disease can suffer from bone disease, bone pain and fractures, soft tissue calcification, vascular calcification and cardiovascular complications. Amgen has rights to develop and sell cinacalcet throughout the world except in Japan, Taiwan and China, where the compound was licensed to Kirin Brewery. Kirin is developing it as KRN 1493 in phase II clinical studies in Japan. In December 2001, commencement of a phase III clinical trial with cinacalcet for the treatment of secondary HPT, triggered a 3 million US dollars milestone payment to NPS Pharmaceuticals. In September 2003, submission of an NDA to the US FDA for cinacalcet for secondary HPT will be followed by a milestone payment of 6 million US dollars to NPS. NPS, Kirin and Amgen were also developing another compound, tecalcet, for HPT, but that project has been discontinued in favour of cinacalcet. In September 2003, Amgen submitted an NDA to the US FDA for secondary HPT in patients with chronic kidney disease. In April 2003, Amgen announced positive results from a phase III clinical trial with cinacalcet in patients with secondary HPT. In a clinical study in patients on dialysis suffering from the effects of chronically elevated levels parathyroid hormone, cinacalcet appeared to be safe and well tolerated and was significantly more effective than placebo. Two more additional efficacy studies with cinacalcet have also been completed. Phase II trials of cinacalcet in dialysis patients with secondary HPT and in patients with primary HPT were successfully completed.

Circulating Plasma MicroRNA-208a as Potential Biomarker of Chronic Indeterminate Phase of Chagas Disease.

PubMed

Linhares-Lacerda, Leandra; Granato, Alessandra; Gomes-Neto, João Francisco; Conde, Luciana; Freire-de-Lima, Leonardo; de Freitas, Elisangela O; Freire-de-Lima, Celio G; Coutinho Barroso, Shana P; Jorge de Alcântara Guerra, Rodrigo; Pedrosa, Roberto C; Savino, Wilson; Morrot, Alexandre

2018-01-01

Chagas cardiomyopathy is the most severe clinical manifestation of chronic Chagas disease. The disease affects most of the Latin American countries, being considered one of the leading causes of morbidity and death in the continent. The pathogenesis of Chagas cardiomyopathy is very complex, with mechanisms involving parasite-dependent cytopathy, immune-mediated myocardial damage and neurogenic disturbances. These pathological changes eventually result in cardiac myocyte hypertrophy, arrhythmias, congestive heart failure and stroke during chronic infection phase. Herein, we show that miR-208a, a microRNA that is a key factor in promoting cardiovascular dysfunction during cardiac hypertrophy processes of heart failure, has its circulating levels increased during chronic indeterminate phase when compared to cardiac (CARD) clinical forms in patients with Chagas disease. In contrast, we have not found altered serum levels of miR-34a, a microRNA known to promote pro-apoptotic role in myocardial infarction during degenerative process of cardiac injuries thus indicating intrinsic differences in the nature of the mechanisms underlying the heart failure triggered by Trypanosoma cruzi infection. Our findings support that the chronic indeterminate phase is a progressive phase involved in the genesis of chagasic cardiopathy and point out the use of plasma levels of miR-208a as candidate biomarker in risk-prediction score for the clinical prognosis of Chagas disease.

Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia.

PubMed

Cohen, Martin H; Williams, Grant; Johnson, John R; Duan, John; Gobburu, Jogarao; Rahman, Atiqur; Benson, Kimberly; Leighton, John; Kim, Sung K; Wood, Rebecca; Rothmann, Mark; Chen, Gang; U, Khin Maung; Staten, Ann M; Pazdur, Richard

2002-05-01

Chronic myelogenous leukemia (CML) results from the breakpoint cluster region-Abl fusion gene product, a tyrosine kinase involved in cell division and apoptosis. Imatinib, an orally administered inhibitor of the breakpoint cluster region-Abl tyrosine kinase, is capable of blocking proliferation and inducing apoptosis in CML cell lines. In this report, we describe the preclinical profile of imatinib and the data submitted in the New Drug Application that led to its marketing approval. Chemistry manufacturing and controls, animal toxicology, and biopharmaceutical data are described. Results of Phase I and Phase II clinical studies in patients with CML in blast crisis (CML-BC), in accelerated phase (CML-AP), and in chronic phase disease-resistant or intolerant to IFN-alpha (CML-CP) are summarized. The basis for marketing approval and postmarketing commitments by the pharmaceutical company are discussed. Toxicology studies in the rat, dog, and monkey show the hematological, renal, and hepatobiliary toxicity of imatinib. Pharmacokinetic studies in patients with CML demonstrate 98% imatinib bioavailability. The elimination half-lives of the parent drug and the major active metabolite, CGP74588, from plasma are approximately 18 and 40 h, respectively. Approximately 81% of the drug is eliminated in 7 days, 68% in the feces and 13% in the urine. Cytochrome P-450 3A4 is the main enzyme responsible for imatinib metabolism. Phase I and II clinical studies were conducted. The Phase I study, in 83 CML patients, evaluated oral imatinib doses from 25 to 1000 mg/day. Dose-limiting toxicity was not observed. The three Phase II studies, in CML-CP, CML-AP, and CML-BC, enrolled 1027 patients. CML-CP patients received 400 mg/day imatinib, whereas CML-AP and CML-BC patients generally received 600 mg/day imatinib. Primary study endpoints were cytogenetic response rate (CML-CP) and hematological response rate (CML-AP and CML-BC). The cytogenetic response rate for CML-CP patients was 49%. The hematological response rate of CML-AP and CML-BC patients was 63 and 26%, respectively. The most common imatinib adverse events were nausea, vomiting, myalgia, edema, and diarrhea. Elevated liver enzymes and/or bilirubin were reported in 27 patients (2.6%). On May 10, 2001, imatinib mesylate (Gleevec, formerly known as STI-571 and Glivec), manufactured and distributed by Novartis Pharmaceuticals, East Hanover, NJ, was approved by the United States Food and Drug Administration for the treatment of CML in three clinical settings: CML-BC, CML-AP, and CML-CP. This report summarizes the Food and Drug Administration's review of the New Drug Application.

MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: the association between MDM2 promoter genotype and disease susceptibility, age of onset, and blast-free survival in chronic phase patients receiving imatinib.

PubMed

Liu, Yi-Chang; Hsiao, Hui-Hua; Yang, Wen-Chi; Liu, Ta-Chih; Chang, Chao-Sung; Yang, Ming-Yu; Lin, Pai-Mei; Hsu, Jui-Feng; Lee, Ching-Ping; Lin, Sheng-Fung

2014-12-01

The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are associated with alternation of p53 activity, however the association regarding CML susceptibility and BP transformation under imatinib treatment is unclear. The MDM2 SNP309 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing from 116 CML patients, including 104 in the CP at diagnosis, and 162 healthy Taiwanese controls. The p53 R72P polymorphism was examined in all CML patients. The SNP309 G/G genotype was associated with an increased risk of CML susceptibility (OR: 1.82, 95% CI: 1.03-3.22, P = 0.037), and an earlier age of disease onset (log-rank P = 0.005) compared with the T/T + T/G genotypes. Higher MDM2 mRNA expression was found in G/G genotype compared with T/T (P = 0.034) and T/T + T/G (P = 0.056) genotypes. No associations were found between the p53 R72P genotypes and clinical parameters and survival outcomes. Among 62 CP patients receiving imatinib as first-line therapy, the G/G genotype was associated with a shorter blast-free survival (log-rank P = 0.048) and more clonal evolution compared with the T/T + T/G genotypes. In patients with advanced diseases at diagnosis, the G/G genotype was associated with a poor overall survival (log-rank P = 0.006). Closely monitoring CML patients harboring the G/G genotype and further large-scale studies are warranted. © 2013 Wiley Periodicals, Inc.

Effect of free radical scavenger, edaravone, for patients with carbon monoxide poisoning.

PubMed

Mori, Kiyofumi; Beppu, Takaaki; Fujisawa, Yutaka; Onodera, Makoto; Ogasawara, Kuniaki; Sasaki, Makoto; Ehara, Shigeru; Sakai, Akio; Endo, Shigeatsu

2015-12-01

Chronic neurological symptoms after carbon monoxide (CO) poisoning are caused by various biological processes in the damaged brain, with free radicals playing roles as mediators in establishing pathological processes leading to chronic neurological symptoms under CO poisoning. This study aimed to clarify the effects of a free radical scavenger, edaravone, in patients with CO poisoning. We retrospectively compared two groups comprising patients treated with hyperbaric oxygenation alone (Group A, n=25) or edaravone in addition to hyperbaric oxygenation (Group B, n=25). Edaravone was administrated intravenously at 30 mg every 12h for 7 days. Patient characteristics, general conditions on admission, and frequency of chronic neurological symptoms were compared between groups. Among patients showing chronic neurological symptoms, cognitive function and daily activity were also compared between groups. No significant differences in characteristics or general conditions on admission were identified between groups. In Group B, no patients presented with marked complications caused by edaravone. Although chronic persisting symptoms were less frequent in Group B (n=1, 0.04%) than in Group A (n=5, 20%), this difference was not significant. In the 11 patients showing chronic symptoms, scores for cognitive function and daily activity in the chronic phase were better in Group B than in Group A, but no significant differences were apparent. The present results suggest that edaravone represents a tolerable and feasible treatment for CO-poisoned patients. Further studies are needed to clarify whether edaravone can favorably influence chronic neurological symptoms caused by CO poisoning. Copyright © 2015 Elsevier B.V. All rights reserved.

Home-based nerve stimulation to enhance effects of motor training in patients in the chronic phase after stroke: a proof-of-principle study.

PubMed

Dos Santos-Fontes, Renata Laurenti; Ferreiro de Andrade, Karina Nocelo; Sterr, Annette; Conforto, Adriana Bastos

2013-01-01

Somatosensory stimulation in the form of repetitive peripheral nerve stimulation (RPSS) is a promising strategy to improve motor function of the upper limb in chronic stroke. Home-based RPSS may be an alternative to hospital-based RPSS. To investigate the feasibility and safety of an innovative program of home-based RPSS combined with motor training and to collect preliminary data on the efficacy of this program to enhance hand motor function in patients in the chronic phase after stroke. Twenty patients were randomized to either active or sham RPSS associated with daily motor training performed at home over 4 consecutive weeks. All the patients were able to perform tasks of the Jebsen-Taylor Test (JTT). The primary outcome measures were feasibility, evaluated by self-reported compliance with the intervention, and safety (adverse events). Secondary outcomes comprised improvements in hand function in the JTT after end of treatment and after a 4-month follow-up period. There were no relevant adverse events. Compliance with RPSS and motor training was significantly greater in the active group than in the sham group. Upper extremity performance improved significantly more in the active group compared with the sham group at the end of treatment. This difference remained significant 4 months later, even when differences in compliance with motor training were considered. Home-based active RPSS associated with motor training was feasible, was safe, and led to long-lasting enhancement of paretic arm performance in the chronic phase after stroke for those who can perform the JTT. These results point to the need for an efficacy trial.

Primary distal femur T-cell lymphoma after allogeneic haematopoietic stem cell transplantation for chronic myeloid leukaemia: a rare case report and literature review.

PubMed

Han, Qiaoyan; Sun, Miao; Wu, Lingyu; Chen, Jing; Wang, Wei; Liu, Chunhua; Chen, Haoyue; Du, Guibin

2014-04-01

Post-transplant lymphoproliferative disorders originating from T lymphocytes are a rare complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) that are not usually associated with Epstein-Barr virus infection. A male patient diagnosed at the age of 15 years with chronic myeloid leukaemia (in the chronic phase) was initially treated with oral hydroxyurea. The disease entered an accelerated phase when the patient was 22 years old. Complete remission was achieved after one course of homoharringtonine and cytarabine. The patient then underwent human leucocyte antigen-matched sibling donor allo-HSCT. Just over 6.5 years after the allo-HSCT, a second primary tumour was located in the distal femur and diagnosed as T-cell non-Hodgkin's lymphoma (stage IV, group B). This was treated with various chemotherapy and radiotherapy regimens, but the outcomes were poor and the disease progressed. The T-cell lymphoma invaded many sites, including the skeleton, spleen and skin, and the patient died within 8 months of the diagnosis. This current case report highlights the need for the early detection and prevention of subsequent primary malignancies after allo-HSCT.

Developing and Translating a New Model for Teaching Empowerment Into Routine Chronic Care Management

PubMed Central

Wallace, Carolyn A; Pontin, David; Dokova, Klara; Mikkonen, Irma; Savage, Eileen; Koskinen, Liisa

2017-01-01

Background: Health professional education has been criticized for not integrating patient expertise into professional curricula to develop professional skills in patient empowerment. Objective: To develop and translate a new expert patient-centered model for teaching empowerment into professional education about routine chronic care management. Methods: Eight Finnish patients (known as expert patients), 31 students, and 11 lecturers from 4 European countries participated in a new pilot intensive educational module. Thirteen focus groups, artefacts, and an online student evaluation were analyzed using a thematic analysis and triangulated using a meta-matrix. Results: A patient-centered pedagogical model is presented, which describes 3 phases of empowerment: (1) preliminary work, (2) the elements of empowerment, and (3) the expected outcomes. These 3 phases were bound by 2 cross-cutting themes “time” and “enabling resources.” Conclusion: Patient expertise was embedded into the new module curriculum. Using an example of care planning, and Pentland and Feldman’s theory of routine organization, the results are translated into a patient-centered educational model for teaching empowerment to health profession students. PMID:29582009

Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis: a randomized, double-blind trial.

PubMed

Hordinsky, Maria; Fleischer, Alan; Rivers, Jason K; Poulin, Yves; Belsito, Donald; Hultsch, Thomas

2010-08-01

Chronic hand dermatitis is common and difficult to treat. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group. Copyright 2010 S. Karger AG, Basel.

Clinical Efficacy and Safety of First-Line Dasatinib Therapy and the Relevance of Velocity of BCR-ABL1 Transcript Decline for Achievement of Molecular Responses in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Report from the Juntendo Yamanashi Cooperative Study Group.

PubMed

Takaku, Tomoiku; Iriyama, Noriyoshi; Mitsumori, Toru; Sato, Eriko; Gotoh, Akihiko; Kirito, Keita; Noguchi, Masaaki; Koike, Michiaki; Sakamoto, Junichi; Oba, Koji; Komatsu, Norio

2018-01-01

The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels. Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated. These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy. © 2017 S. Karger AG, Basel.

Health-related quality of life and health care use in cancer survivors compared with patients with chronic diseases.

PubMed

Heins, Marianne J; Korevaar, Joke C; Hopman, Petra E P C; Donker, Gé A; Schellevis, François G; Rijken, Mieke P M

2016-03-15

The number of cancer survivors is steadily increasing and these patients often experience long-lasting health problems. To make care for cancer survivors sustainable for the future, it would be relevant to put the effects of cancer in this phase into perspective. Therefore, the authors compared health-related quality of life (HRQOL) and health care use among cancer survivors with that of patients with chronic diseases. Patients diagnosed at age >18 years with a cancer with a 5-year survival rate > 20% and no distant metastases at the time of diagnosis and patients aged >18 years with physician-diagnosed somatic chronic diseases without cancer were sent a questionnaire. HRQOL was measured with the RAND-36, a measure of HRQOL. Self-reported health care use was measured for general practitioner care, specialist care, rehabilitative care, physical therapy, ambulatory mental health care, and occupational health care. A total of 601 cancer survivors and 1052 patients with chronic diseases without cancer were included in the current study. Multimorbidity was observed in 63% of the cancer survivors and 61% of the patients with chronic diseases. The HRQOL of the cancer survivors was significantly better than that of patients with chronic diseases after adjustment for age and sex. For the mental functioning subscale, no significant differences were found between the 2 groups. Cancer survivors were found to be less likely to have visited a general practitioner or cardiologist compared with patients with chronic diseases. When considering physical HRQOL and health care use, cancer survivors appear to fare better than the average patient with chronic diseases. No difference in mental functioning was observed in the current study. © 2016 American Cancer Society.

Decreased short-interval intracortical inhibition correlates with better pinch strength in patients with stroke and good motor recovery.

PubMed

Ferreiro de Andrade, Karina Nocelo; Conforto, Adriana Bastos

2018-02-06

Deeper short-interval intracortical inhibition (SICI), a marker of GABA A activity, correlates with better motor performance in patients with moderate to severe hand impairments in the chronic phase after stroke. We evaluated the correlation between SICI in the affected hemisphere and pinch force of the paretic hand in well-recovered patients. We also investigated the correlation between SICI and pinch force in controls. Twenty-two subjects were included in the study. SICI was measured with a paired-pulse paradigm. The correlation between lateral pinch strength and SICI was assessed with Spearman's rho. There was a significant correlation (rho = 0.69, p = 0.014) between SICI and pinch strength in patients, but not in controls. SICI was significantly deeper in patients with greater hand weakness. These preliminary findings suggest that decreased GABA A activity in M1 AH correlates with better hand motor performance in well-recovered subjects with stroke in the chronic phase. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic daily headache: stress and impact on the quality of life.

PubMed

Galego, José Carlos Busto; Moraes, Avelina Maria; Cordeiro, José Antonio; Tognola, Waldir Antonio

2007-12-01

To evaluate the stress presence and its influence in the quality of life of patients with chronic daily headache (CDH). A hundred patients with at least 18 years old, with primary headache with duration greater than 4 hours a day, and frequency of 15 or more days monthly for at least three months were studied. Lipp's Inventory of Stress Symptoms and the Medical Outcomes Study Short Form (SF-36) were used. Stress was observed in 90% of the patients; nearly half of them was in the phase almost exhaustion. Patients with stress when compared with the ones with no stress presented significantly lower scores in all the domains of SF-36; except in physical functioning. The resistance phase presented scores significantly higher than almost exhaustion; except for bodily pain. The majority of the patients presented stress with significant reduction in their quality of life. Consequently, the stress could be related with both the development and the maintenance of CDH.

Nilotinib after imatinib first-line: a real-life longitudinal cohort of patients with chronic myeloid leukaemia in chronic phase.

PubMed

Cony-Makhoul, Pascale; Gardembas, Martine; Coiteux, Valérie; Carpentier, Nathalie; Pommier, Cécile; Violet, Isabelle; Quittet, Philippe; Berger, Marc G

2018-02-01

This prospective, observational study enrolled 150 adult patients with chronic myeloid leukaemia (CML) in chronic phase (CP) treated with nilotinib as second-line after imatinib, in a real life setting in France. Two-thirds of patients switched to nilotinib treatment due to lack of imatinib efficacy. Of 146 evaluable patients, 16 (11·0%) (95% confidence interval: 6·4-17·2%) achieved uMR 4 , defined as undetectable molecular disease in cDNA with MR 4 sensitivity (≥10 000 ABL1 transcripts) at 18 months and confirmed at 24 months (primary endpoint). Among patients without major molecular response (MMR) or deep molecular response (DMR) at study entry, 66·3% achieved MMR and 44·2% DMR within a median of 5·7 and 6·24 months, respectively. Fifty-three patients (36·3%) have prematurely terminated the study before 24 months of follow-up, primarily due to nilotinib treatment discontinuation (n = 43; 29·5%), mainly motivated by treatment intolerance (n = 27; 18·5%) and inefficacy (n = 10; 6·8%). The most frequent extra-haematological adverse events (AEs) reported as related to treatment with nilotinib were pruritus (16·4%), asthenia (13·7%) and dry skin (13·0%). Ischaemic cardiovascular AEs were reported in 18 patients (12·3%). This French nationwide large cohort adds valuable information to the body of evidence on the efficiency and safety of nilotinib in the treatment of patients with CP-CML. © 2017 John Wiley & Sons Ltd.

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa.

PubMed

Itonaga, Hidehiro; Tsushima, Hideki; Hata, Tomoko; Matsuo, Emi; Imanishi, Daisuke; Imaizumi, Yoshitaka; Kawaguchi, Yasuhisa; Fukushima, Takuya; Doi, Yuko; Mori, Sayaka; Kamihira, Shimeru; Tomonaga, Masao; Miyazaki, Yasushi

2012-02-01

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.

Simultaneous regression of Philadelphia chromosome and multiple nonrecurrent clonal chromosomal abnormalities with imatinib mesylate in a patient autografted 22 years before for chronic myelogenous leukemia.

PubMed

Van Den Akker, J; Coppo, P; Portnoï, M F; Barbu, V; Bories, D; Gorin, N C

2007-09-01

A 31-year-old patient developed chronic myelogenous leukemia (CML) in November, 1983. In November 1984, following a diagnosis of acceleration, he received an autologous hemopoietic transplant after conditioning with cyclophosphamide and total body irradiation. The autologous marrow was purged with mafosfamide. Over 20 years, the patient remained in chronic phase of CML. Multiple nonrecurrent clonal chromosomal abnormalities appeared leading to a very complex karyotype, including among others involvement of chromosomes 1, 7, 9, 13, 19, and X. Fluorescent in situ hybridization showed that the two chromosomes 9 were involved. Acute myeloid crisis was diagnosed in February, 2004. Treatment with imatinib mesylate resulted within 6 months in a total disappearance of all chromosomal abnormalities with a complete cytogenetic and molecular response, which persists 3 years later. We question whether the ex vivo purging procedure with mafosfamide has favored the occurrence of these particular cytogenetic abnormalities (with no independent oncogenic potential) within the original leukemic stem cell pool. It remains unclear whether the autologous transplantation has indeed resulted into some prolongation of the duration of the chronic phase, which lasted for 20 years. At time of acute crisis, the dramatic response to imatinib mesylate leading to a complete cytogenetic and molecular response is noteworthy.

Manual Physical Therapists' Use of Biopsychosocial History Taking in the Management of Patients with Back or Neck Pain in Clinical Practice

PubMed Central

Oostendorp, Rob A. B.; Elvers, Hans; Mikołajewska, Emilia; Laekeman, Marjan; van Trijffel, Emiel; Samwel, Han; Duquet, William

2015-01-01

Objective. To develop and evaluate process indicators relevant to biopsychosocial history taking in patients with chronic back and neck pain. Methods. The SCEBS method, covering the Somatic, Psychological (Cognition, Emotion, and Behavior), and Social dimensions of chronic pain, was used to evaluate biopsychosocial history taking by manual physical therapists (MPTs). In Phase I, process indicators were developed while in Phase II indicators were tested in practice. Results. Literature-based recommendations were transformed into 51 process indicators. Twenty MTPs contributed 108 patient audio recordings. History taking was excellent (98.3%) for the Somatic dimension, very inadequate for Cognition (43.1%) and Behavior (38.3%), weak (27.8%) for Emotion, and low (18.2%) for the Social dimension. MTPs estimated their coverage of the Somatic dimension as excellent (100%), as adequate for Cognition, Emotion, and Behavior (60.1%), and as very inadequate for the Social dimension (39.8%). Conclusion. MTPs perform screening for musculoskeletal pain mainly through the use of somatic dimension of (chronic) pain. Psychological and social dimensions of chronic pain were inadequately covered by MPTs. Furthermore, a substantial discrepancy between actual and self-estimated use of biopsychosocial history taking was noted. We strongly recommend full implementation of the SCEBS method in educational programs in manual physical therapy. PMID:25945358

Protease inhibitors-based therapy induces acquired spherocytic-like anaemia and ineffective erythropoiesis in chronic hepatitis C virus patients.

PubMed

Lupo, Francesca; Russo, Roberta; Iolascon, Achille; Ieluzzi, Donatella; Siciliano, Angela; Toniutto, Pierluigi; Matté, Alessandro; Piovesan, Sara; Raffetti, Elena; Turrini, Francesco; Dissegna, Denis; Donato, Francesco; Alberti, Alfredo; Zuliani, Valeria; Fattovich, Giovanna; De Franceschi, Lucia

2016-01-01

The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg-interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. We studied 59 patients with chronic HCV genotype-1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. We found early acute normochromic normocytic haemolytic anaemia (4-8 weeks) followed by a late macrocytic hypo-regenerative anaemia with inappropriate low reticulocyte count (12-24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane-cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic-like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions

PubMed Central

Mehta, Veela; Pei, Wei; Yang, Grant; Li, Suyang; Swamy, Eashwar; Boster, Aaron; Schmalbrock, Petra; Pitt, David

2013-01-01

MRI phase imaging in multiple sclerosis (MS) patients and in autopsy tissue have demonstrated the presence of iron depositions in white matter lesions. The accumulation of iron in some but not all lesions suggests a specific, potentially disease-relevant process, however; its pathophysiological significance remains unknown. Here, we explore the role of lesional iron in multiple sclerosis using multiple approaches: immunohistochemical examination of autoptic MS tissue, an in vitro model of iron-uptake in human cultured macrophages and ultra-highfield phase imaging of highly active and of secondary progressive MS patients. Using Perls' stain and immunohistochemistry, iron was detected in MS tissue sections predominantly in non-phagocytosing macrophages/microglia at the edge of established, demyelinated lesions. Moreover, iron-containing macrophages but not myelin-laden macrophages expressed markers of proinflammatory (M1) polarization. Similarly, in human macrophage cultures, iron was preferentially taken up by non-phagocytosing, M1-polarized macrophages and induced M1 (super) polarization. Iron uptake was minimal in myelin-laden macrophages and active myelin phagocytosis led to depletion of intracellular iron. Finally, we demonstrated in MS patients using GRE phase imaging with ultra-highfield MRI that phase hypointense lesions were significantly more prevalent in patients with active relapsing than with secondary progressive MS. Taken together, our data provide a basis to interpret iron-sensitive GRE phase imaging in MS patients: iron is present in non-phagocytosing, M1-polarized microglia/macrophages at the rim of chronic active white matter demyelinating lesions. Phase imaging may therefore visualize specific, chronic proinflammatory activity in established MS lesions and thus provide important clinical information on disease status and treatment efficacy in MS patients. PMID:23516409

Achievement of Target Blood Pressure Levels among Japanese Workers with Hypertension and Healthy Lifestyle Characteristics Associated with Therapeutic Failure.

PubMed

Kudo, Nagako; Yokokawa, Hirohide; Fukuda, Hiroshi; Sanada, Hironobu; Miwa, Yuichi; Hisaoka, Teruhiko; Isonuma, Hiroshi

2015-01-01

Few studies have examined Japanese with regard to the achievement rates for target blood pressure levels, or the relationship between these rates and healthy lifestyle characteristics in patients with hypertension as defined by the newly established hypertension management guidelines (JSH2014). The aim of this study was to elucidate achievement rates and examine healthy lifestyle characteristics associated with achievement status among Japanese. This cross-sectional study, conducted in January-December 2012, examined blood pressure control and healthy lifestyle characteristics in 8,001 Japanese workers with hypertension (mean age, 57.0 years; 78.8% were men) who participated in a workplace health checkup. Data were collected from workplace medical checkup records and participants' self-administered questionnaires. We divided into 5 groups [G1; young, middle-aged, and early-phase elderly patients (65-74 years old) without diabetes mellitus or chronic kidney disease (CKD) (<140/90 mmHg), G2; late-phase elderly patients (≥75 years old) without diabetes mellitus or CKD (<150/90 mmHg), G3; diabetic patients (<130/80 mmHg), G4; patients with CKD (<130/80 mmHg), and G5; patients with cerebrovascular and/or coronary artery diseases (<140/90 mmHg)] according to JSH2014. And then, achievement rates were calculated in each group. Multivariate analysis identified healthy lifestyle characteristics associated with "therapeutic failure" of target blood pressure. Target blood pressures were achieved by 60.2% of young, middle-aged, and early-phase elderly patients (G1), 71.4% of late-phase elderly patients (G2), 30.5% of diabetic patients (G3), 33.4% of those with chronic kidney disease (G4), and 66.0% of those with cerebrovascular and/or coronary artery diseases (G5). A body mass index of 18.5-24.9 and non-daily alcohol consumption were protective factors, and adequate sleep was found to contribute to therapeutic success. We found low achievement rates for treatment goals among patients with chronic kidney disease and diabetes mellitus. Maintaining an ideal body weight and adequate alcohol consumption may help with blood pressure control. Lifestyle modification may be necessary for better management of hypertension.

Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study.

PubMed

Stilgenbauer, Stephan; Eichhorst, Barbara; Schetelig, Johannes; Coutre, Steven; Seymour, John F; Munir, Talha; Puvvada, Soham D; Wendtner, Clemens-Martin; Roberts, Andrew W; Jurczak, Wojciech; Mulligan, Stephen P; Böttcher, Sebastian; Mobasher, Mehrdad; Zhu, Ming; Desai, Monali; Chyla, Brenda; Verdugo, Maria; Enschede, Sari Heitner; Cerri, Elisa; Humerickhouse, Rod; Gordon, Gary; Hallek, Michael; Wierda, William G

2016-06-01

Deletion of chromosome 17p (del[17p]) in patients with chronic lymphocytic leukaemia confers very poor prognosis when treated with standard chemo-immunotherapy. Venetoclax is an oral small-molecule BCL2 inhibitor that induces chronic lymphocytic leukaemia cell apoptosis. In a previous first-in-human study of venetoclax, 77% of patients with relapsed or refractory chronic lymphocytic leukaemia achieved an overall response. Here we aimed to assess the activity and safety of venetoclax monotherapy in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia. In this phase 2, single-arm, multicentre study, we recruited patients aged 18 years and older with del(17p) relapsed or refractory chronic lymphocytic leukaemia (as defined by 2008 Modified International Workshop on Chronic Lymphocytic Leukemia guidelines) from 31 centres in the USA, Canada, UK, Germany, Poland, and Australia. Patients started once daily venetoclax with a weekly dose ramp-up schedule (20, 50, 100, 200, 400 mg) over 4-5 weeks. Patients were then given daily 400 mg continuous dosing until disease progression or discontinuation for another reason. The primary endpoint was the proportion of patients achieving an overall response, assessed by an independent review committee. Activity and safety analyses included all patients who received at least one dose of study drug (per protocol). This study is registered with ClinicalTrials.gov, number NCT01889186. Follow-up is ongoing, and patients are still receiving treatment. Between May 27, 2013, and June 27, 2014, 107 patients were enrolled into the study. At a median follow-up of 12·1 months (IQR 10·1-14·2), an overall response by independent review was achieved in 85 (79·4%; 95% CI 70·5-86·6) of 107 patients. The most common grade 3-4 adverse events were neutropenia (43 [40%]), infection (21 [20%]), anaemia (19 [18%]), and thrombocytopenia (16 [15%]). Serious adverse events occurred in 59 (55%) patients, irrespective of their relationship to treatment, with the most common (≥5% of patients) being pyrexia and autoimmune haemolytic anaemia (seven [7%] each), pneumonia (six [6%]), and febrile neutropenia (five [5%]). 11 patients died in the study within 30 days of the last dose of venetoclax; seven due to disease progression and four from an adverse event (none assessed as treatment related). Results of this trial show that venetoclax monotherapy is active and well tolerated in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia, providing a new therapeutic option for this very poor prognosis population. Additionally, in view of the distinct mechanism-of-action of venetoclax, combinations or sequencing with other novel targeted agents should be investigated to further advance treatment of del(17p) chronic lymphocytic leukaemia. AbbVie and Genentech. Copyright © 2016 Elsevier Ltd. All rights reserved.

Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2018-01-17

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Indolent Non-Hodgkin Lymphoma; Lymphoma; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Non-Hodgkin Lymphoma

The perceptions and perspectives of patients and health care providers on chronic diseases management in rural South Africa: a qualitative study.

PubMed

Maimela, Eric; Van Geertruyden, Jean-Pierre; Alberts, Marianne; Modjadji, Sewela E P; Meulemans, Herman; Fraeyman, Jesicca; Bastiaens, Hilde

2015-04-08

Preventive health care represents the future for health care delivery in South Africa to improve management of chronic diseases as this has been implemented for some time in several countries to tackle the increasing burden of chronic diseases. Individual person's health is unique, as they move in and out of chronic and acute health care phases, there is need to integrate chronic and acute care constructs to improve continuity of care and maximize health and improve wellbeing. The aim of this study was to determine the perceptions and perspectives of chronic patients' and nurses regarding chronic disease management in terms of barriers, facilitators and their experiences. To meet our aim we used qualitative methods involving the collection of information by means of focus group discussions in Dikgale Health and Demographic Surveillance System (HDSS). All data was recorded, transcribed verbatim and analysed using data-driven thematic analysis. Our study showed that chronic disease patients have a first contact with health care professionals at the primary health care level in the study area. The main barriers mentioned by both the health care workers and chronic disease patients are lack of knowledge on chronic diseases, shortage of medication and shortage of nurses in the clinics which causes patients to wait for a long periods in a clinic. Health care workers are poorly trained on the management of chronic diseases. Lack of supervision by the district and provincial health managers together with poor dissemination of guidelines has been found to be a contributing factor to lack of knowledge in nurses among the clinics within the study area. Both patients and nurses mentioned the need to involve community health workers and traditional healers and integrate their services in order to early detect and manage chronic diseases in the community. Nurses and chronic disease patients mentioned similar barriers to chronic disease management. Concerted action is needed to strengthen the delivery of medications at the clinics, improve the chronic disease knowledge for both nurses and patients by conducting in-service trainings or workshops, increase the involvement of community health workers and establish a link (through formal referral system) with traditional healers.

Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities.

PubMed

Gish, Robert G; Given, Bruce D; Lai, Ching-Lung; Locarnini, Stephen A; Lau, Johnson Y N; Lewis, David L; Schluep, Thomas

2015-09-01

The host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the "high replicative, low inflammatory" phase now replacing what was formerly termed the "immune tolerant" phase, and the "nonreplicative phase" replacing what was formerly termed the "inactive carrier" phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate's immune system, new findings on trained immunity show that the host is already somewhat "matured" following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of 'cure' are emerging, such as 'functional' and 'virological' cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." Copyright © 2015 Elsevier B.V. All rights reserved.

Relation between brain temperature and white matter damage in subacute carbon monoxide poisoning

PubMed Central

Fujiwara, Shunrou; Yoshioka, Yoshichika; Matsuda, Tsuyoshi; Nishimoto, Hideaki; Ogawa, Akira; Ogasawara, Kuniaki; Beppu, Takaaki

2016-01-01

In the previous studies, carbon monoxide (CO) poisoning showed an imbalance between cerebral perfusion and metabolism in the acute phase and the brain temperature (BT) in these patients remained abnormally high from the acute to the subacute phase. As observed in chronic ischemic patients, BT can continuously remain high depending on impairments of cerebral blood flow and metabolism; this is because heat removal and production system in the brain may mainly be maintained by the balance of these two factors; thus, cerebral white matter damage (WMD) affecting normal metabolism may affect the BT in patients with CO poisoning. Here, we investigated whether the BT correlates with the degree of WMD in patients with subacute CO-poisoning. In 16 patients with subacute CO-poisoning, the BT and degree of WMD were quantitatively measured by using magnetic resonance spectroscopy and the fractional anisotropy (FA) value from diffusion tensor imaging dataset. Consequently, the BT significantly correlated with the degree of WMD. In particular, BT observed in patients with delayed neuropsychiatric sequelae, a crucial symptom with sudden-onset in the chronic phase after CO exposure, might indicate cerebral hypo-metabolism and abnormal hemodynamics like “matched perfusion,” in which the reduced perfusion matches the reduced metabolism. PMID:27819312

Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice

PubMed Central

Tajerian, Maral; Leu, David; Yang, Phillip; Huang, Ting Ting; Kingery, Wade S; Clark, J David

2015-01-01

Background Complex regional pain syndrome (CRPS) is a painful, disabling and often chronic condition, where many patients transition from an acute phase with prominent peripheral neurogenic inflammation to a chronic phase with evident central nervous system (CNS) changes. Ketamine is a centrally-acting agent believed to work through blockade of N-methyl-D-aspartate (NMDA) receptors and is being increasingly used for the treatment of refractory CRPS, although the basis for the drug’s effects and efficacy at different stages of the syndrome remain unclear. Methods We used a mouse model of CRPS (n=8–12/group) involving tibia fracture/cast immobilization to test the efficacy of ketamine (2 mg/kg/day; 7 days) or vehicle infusion during acute (3weeks [3w] post-fracture) and chronic (7w post-fracture) stages. Results Acute phase fracture mice displayed elevated limb temperature, edema and nociceptive sensitization that were not reduced by ketamine. Fracture mice treated with ketamine during the chronic phase showed reduced nociceptive sensitization that persisted beyond completion of the infusion. During this chronic phase, ketamine also reduced latent nociceptive sensitization and improved motor function at 18 weeks post-fracture. No side effects of the infusions were identified. These behavioral changes were associated with altered spinal astrocyte activation and expression of pain-related proteins including NMDA receptor 2b (NR2b), Ca2+/calmodulin-dependent protein kinase ii (CaMK2), and brain-derived neurotrophic factor (BNDF). Conclusions Collectively, these results demonstrate that ketamine is efficacious in the chronic, but not acute stages of CRPS, suggesting that the centrally-acting drug is relatively ineffective in early CRPS when peripheral mechanisms are more critical for supporting nociceptive sensitization. PMID:26492479

The Impact of Big Data on Chronic Disease Management.

PubMed

Bhardwaj, Niharika; Wodajo, Bezawit; Spano, Anthony; Neal, Symaron; Coustasse, Alberto

Population health management and specifically chronic disease management depend on the ability of providers to prevent development of high-cost and high-risk conditions such as diabetes, heart failure, and chronic respiratory diseases and to control them. The advent of big data analytics has potential to empower health care providers to make timely and truly evidence-based informed decisions to provide more effective and personalized treatment while reducing the costs of this care to patients. The goal of this study was to identify real-world health care applications of big data analytics to determine its effectiveness in both patient outcomes and the relief of financial burdens. The methodology for this study was a literature review utilizing 49 articles. Evidence of big data analytics being largely beneficial in the areas of risk prediction, diagnostic accuracy and patient outcome improvement, hospital readmission reduction, treatment guidance, and cost reduction was noted. Initial applications of big data analytics have proved useful in various phases of chronic disease management and could help reduce the chronic disease burden.

Distribution of IgA subclass response to Coxiella burnetii in patients with acute and chronic Q fever.

PubMed

Camacho, M T; Outschoorn, I; Echevarría, C; Kovácová, E; Yebra, M; Maté, I; Auffray, P; Téllez, A

1998-07-01

The progression of Coxiella burnetii infection to acute or chronic Q fever has been attributed to biological characteristics of the bacterium and to the host immune response. We measured whether serum levels of total and specific subclasses IgA1 and IgA2 could be correlated with the course of disease in acute and chronic Q fever infections, and with the occurrence of endocarditis. In patients with chronic infection, total IgA2 levels were significantly increased. Q-fever-specific IgA1 antibodies were detectable in both acute and chronic infections, but only patients with endocarditis had IgA2 antibodies to C. burnetii phase II antigens. These findings indicate that the measurement of IgA subclasses may be a useful aid in the serological diagnosis of Q fever. Our results reinforce the idea that immunologically mediated host factors are important in the pathogenesis of Q fever and in the disease outcome of this infection. Copyright 1998 Academic Press.

Diagnostic criteria of traumatic central cord syndrome. Part 3: descriptive analyses of neurological and functional outcomes in a prospective cohort of traumatic motor incomplete tetraplegics.

PubMed

Pouw, M H; van Middendorp, J J; van Kampen, A; Curt, A; van de Meent, H; Hosman, A J F

2011-05-01

Prospective multicenter cohort study. To compare the neurological recovery and functional outcomes between traumatic central cord syndrome (TCCS) patients and motor incomplete tetraplegic patients. European Multicenter Study of human spinal cord injury. In 248 traumatic motor incomplete tetraplegics, initial phase (0-15 days) American Spinal Injury Association (ASIA) impairment grading, upper and lower extremity motor scores (UEMS and LEMS), upper and lower sensory scores and chronic phase (6 or 12 months) neurological outcomes were analyzed. In addition, chronic phase self-care and indoor mobility Spinal Cord Independence Measure (SCIM) items were studied. Tetraplegics were subdivided into three groups: (1) non-TCCS group (UEMSLEMS), (2) intermediate-TCCS group (UEMS=(1-9 points)

Methodological considerations, such as directed acyclic graphs, for studying "acute on chronic" disease epidemiology: chronic obstructive pulmonary disease example.

PubMed

Tsai, Chu-Lin; Camargo, Carlos A

2009-09-01

Acute exacerbations of chronic disease are ubiquitous in clinical medicine, and thus far, there has been a paucity of integrated methodological discussion on this phenomenon. We use acute exacerbations of chronic obstructive pulmonary disease as an example to emphasize key epidemiological and statistical issues for this understudied field in clinical epidemiology. Directed acyclic graphs are a useful epidemiological tool to explain the differential effects of risk factor on health outcomes in studies of acute and chronic phases of disease. To study the pathogenesis of acute exacerbations of chronic disease, case-crossover design and time-series analysis are well-suited study designs to differentiate acute and chronic effect. Modeling changes over time and setting appropriate thresholds are important steps to separate acute from chronic phases of disease in serial measurements. In statistical analysis, acute exacerbations are recurrent events, and some individuals are more prone to recurrences than others. Therefore, appropriate statistical modeling should take into account intraindividual dependence. Finally, we recommend the use of "event-based" number needed to treat (NNT) to prevent a single exacerbation instead of traditional patient-based NNT. Addressing these methodological challenges will advance research quality in acute on chronic disease epidemiology.

Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

PubMed Central

Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

2016-01-01

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis. PMID:27048866

Intervention with Formulated Collagen Gel for Chronic Heel Pressure Ulcers in Older Adults with Diabetes.

PubMed

Agosti, Jennifer K; Chandler, Lois A

2015-11-01

Chronic pressure ulcers (PrUs), ulcers that fail to progress through the expected phases of wound healing in a timely fashion, are not only a concern for the patients afflicted with them, but are also a significant burden for the long-term-care facilities in which patients reside. The heel is the second most common location for PrUs. Morbidity and mortality rates for heel PrUs, particularly in the diabetic population, are alarming. Therefore, a consistently effective, cost-conscious, and user-friendly topical treatment for heel ulcers would be welcomed by patients and clinicians. This article describes a marked and rapid improvement in wound granulation in 3 older adult patients following weekly treatment for 8 weeks of chronic (≥1-year duration) heel ulcers with an easy-to-use, cost-effective, topical, formulated collagen gel.

Dasatinib rapidly induces deep molecular response in chronic-phase chronic myeloid leukemia patients who achieved major molecular response with detectable levels of BCR-ABL1 transcripts by imatinib therapy.

PubMed

Shiseki, Masayuki; Yoshida, Chikashi; Takezako, Naoki; Ohwada, Akira; Kumagai, Takashi; Nishiwaki, Kaichi; Horikoshi, Akira; Fukuda, Tetsuya; Takano, Hina; Kouzai, Yasuji; Tanaka, Junji; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

2017-10-01

With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR-ABL1 transcripts. The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy.

A rare case of a three way complex variant positive Philadelphia translocation involving chromosome (9;11;22)(q34;p15;q11) in chronic myeloid leukemia: A case report

PubMed Central

Asif, Muhammad; Hussain, Abrar; Rasool, Mahmood

2016-01-01

The t(9;22)(q34;q11) translocation is present in 90–95% of patients with chronic myeloid leukemia (CML). Variant complex translocations have been observed in 5–8% of CML patients, in which a third chromosome other than (9;22) is involved. Imatinib mesylate is the first line breakpoint cluster region-Abelson gene (BCR/ABL)-targeted oral therapy for CML, and may produce a complete response in 70–80% of CML patients in the chronic phase. In the present study, a bone marrow sample was used for conventional cytogenetic analysis, and the fluorescence in situ hybridization (FISH) test was used for BCR/ABL gene detection. A hematological analysis was also performed to determine the white blood cell (WBC) count, red blood cell count, hemoglobin levels, packed and mean cell volumes, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and platelet values of the patient. The hematological analysis of the patient indicated the increased WBC of 186.5×103 cells/µl, and decreased hemoglobin levels of 11.1 g/dl. The FISH test revealed that 67% cells demonstrated BCR/ABL gene translocation. The patient was treated with 400 mg imatinib mesylate daily, and was monitored at various intervals over a 6-month period. The present study reports the rare case of a patient that demonstrates a three-way Philadelphia chromosome-positive translocation involving 46XY,t(9;11;22)(q34;p15;q11)[10], alongside CML in the chronic phase. The translocation was analyzed using cytogenetic and FISH tests. PMID:27602125

Chronic herpes simplex type-1 encephalitis with intractable epilepsy in an immunosuppressed patient.

PubMed

Laohathai, Christopher; Weber, Daniel J; Hayat, Ghazala; Thomas, Florian P

2016-02-01

Chronic herpes simplex virus type-1 encephalitis (HSE-1) is uncommon. Past reports focused on its association with prior documented acute infection. Here, we describe a patient with increasingly intractable epilepsy from chronic HSE-1 reactivation without history of acute central nervous system infection. A 49-year-old liver transplant patient with 4-year history of epilepsy after initiation of cyclosporine developed increasingly frequent seizures over 3 months. Serial brain magnetic resonance imaging showed left temporoparietal cortical edema that gradually improved despite clinical decline. Herpes simplex virus type-1 (HSV-1) DNA was detected in cerebrospinal fluid by polymerase chain reaction. Cerebrospinal fluid HSV-1&2 IgM was negative. Seizures were controlled after acyclovir treatment, and the patient remained seizure free at 1-year follow-up. Chronic HSE is a cause of intractable epilepsy, can occur without a recognized preceding acute phase, and the clinical course of infection may not directly correlate with neuroimaging changes.

Uncertainty of Acute Stroke Patients: A Cross-sectional Descriptive and Correlational Study.

PubMed

Ni, Chunping; Peng, Jing; Wei, Yuanyuan; Hua, Yan; Ren, Xiaoran; Su, Xiangni; Shi, Ruijie

2018-06-12

Uncertainty is a chronic and pervasive source of psychological distress for patients and plays an important role in the rehabilitation of stroke survivors. Little is known about the level and correlates of uncertainty among patients in the acute phase of stroke. The purposes of this study were to describe the uncertainty of patients in the acute phase of stroke and to explore characteristics of patients associated with that uncertainty. A cross-sectional descriptive and correlational study was conducted with a convenience sample of 451 consecutive hospitalized acute stroke patients recruited from the neurology department of 2 general hospitals of China. Uncertainty was measured using Chinese versions of Mishel Uncertainty in Illness Scale for Adults on the fourth day of patients' admission. The patients had moderately high Mishel Uncertainty in Illness Scale for Adults scores (mean [SD], 74.37 [9.22]) in the acute phase of stroke. A total of 95.2% and 2.9% of patients were in moderate and high levels of uncertainty, respectively. The mean (SD) score of ambiguity (3.05 [0.39]) was higher than that of complexity (2.88 [0.52]). Each of the following characteristics was independently associated with greater uncertainty: functional status (P = .000), suffering from other chronic diseases (P = .000), time since the first-ever stroke (P = .000), self-evaluated economic pressure (P = .000), family monthly income (P = .001), educational level (P = .006), and self-evaluated severity of disease (P = .000). Patients experienced persistently, moderately high uncertainty in the acute phase of stroke. Ameliorating uncertainty should be an integral part of the rehabilitation program. Better understanding of uncertainty and its associated characteristics may help nurses identify patients at the highest risk who may benefit from targeted interventions.

Q fever in the Southern California desert: epidemiology, clinical presentation and treatment.

PubMed

Cone, Lawrence A; Curry, Noel; Shaver, Phillip; Brooks, David; DeForge, James; Potts, Barbara E

2006-07-01

Despite the absence of a natural reservoir for Q fever in the desert of Southern California, six cases have been identified during the past 32 years. During that period of time, two areas have been used by northern sheep ranchers from Idaho and Wyoming to import sheep to an area in the Coachella Valley through 1985. Thereafter, because of housing development, the sheep area was moved to Blythe along the Colorado River. All but two of these patients probably acquired infection by Coxiella burnetii by living or working in close proximity to these grazing areas but not directly involved with the sheep. The shift of infected patients from the Coachella Valley to Blythe (100 miles distant) seems to support that supposition. All patients with acute Q fever developed antibodies primarily to phase II antigen, whereas the only person with chronic Q fever developed phase I antibodies. All patients presented with granulomatous hepatitis. One also had a pulmonary infiltrate, and the single individual with chronic Q fever also had a mitral valve prosthesis, although echocardiography could not define endocarditis. All patients with acute infections responded to 3-5 weeks of therapy with doxycycline, whereas the patient with chronic disease failed 3 years of therapy with combination regimens. Further studies at the Eisenhower Medical Center on the prevalence of infection in Blythe, CA, and elsewhere are anticipated.

The clinical safety of ibrutinib in chronic lymphocytic leukemia.

PubMed

Molica, Stefano

2015-10-01

Ibrutinib , a targeted inhibitor of B-cell receptor signaling, achieved impressive clinical results for patients with chronic lymphocytic leukemia (CLL). These results allowed the approval of ibrutinib for the treatment of patients with CLL who have received at least one prior therapy and those with a 17p deletion regardless of line of therapy. Comprehensive data from either Phase I-II or randomized Phase III studies are analyzed in this article. In addition, we reviewed data on the prevalence and the clinical management of some peculiar toxicities ibrutinib related such as lymphocytosis, major bleeding and atrial fibrillation. Ibrutinib has radically changed the scenery of relapsed/refractory CLL treatment and established an important paradigm in the molecularly targeted approach of this disease. Discontinuation of ibrutinib is rarely due to adverse events related to the drug. Patients who discontinue treatment represent a challenge to the physicians because treatment options are very limited.

Is there any Role for Splenectomy in Adulthood Onset Chronic Immun e Thrombocytopenia in the Era of TPO Receptors Agonists? A Critic al Overview.

PubMed

Vibor, Milunovic; Rogulj, Inga Mandac; Ostojic, Slobodanka Kolonic

2017-07-04

Immune thrombocytopenia (ITP) in adulthood is characterized by chronic relapsing course. Despite the efficacious first line treatment (corticosteroid, intravenous immunoglobulin), majority of patients will enter the chronic phase warranting another treatment approach. Until recently, splenectomy performed in ITP chronic phase represented the standard of care with longterm remissions in more than 70% of patients, but it has never been tested in clinical trials. However, with the advances of our understanding of ITP pathophysiology and the shifting focus on megakaryocyte impairment, novel drugs were introduced in the treatment paradigm, mainly trombopoietin receptor agonists (TPO-RAs); romiplostim and eltrombopag. These TPO-RAs were tested in randomized controlled trials resulting in adequate platelet response with few side effects and less need for additional therapy leading to approval of corresponding regulatory agencies and wide acceptance by hematological community, but however TPO-RAs must be taken continuously to maintain the response. With their onset, the rate of splenectomy in chronic ITP has diminished in modern era. The main aim behind conducting this review is to evaluate the pros and cons of splenectomy compared to TPO-RAs treatment in order to provide the critical overview which may help the practicing clinician in managing often challenging cases of chronic ITP. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of phase proprioceptive training on balance in patients with chronic stroke.

PubMed

Chae, Seung Hun; Kim, You Lim; Lee, Suk Min

2017-05-01

[Purpose] This study aimed to investigate the effect of phase proprioceptive training on balance in patients with chronic stroke. [Subjects and Methods] Participants included 30 patients with stroke who were randomly assigned to the proprioceptive training group (n=15) or control group (n=15). Participants in the proprioceptive training group underwent proprioceptive training and received general physical therapy each for a total of 20 thirty-minute sessions, five times per week, during a period of four weeks; the control group received general physical therapy for a total of 20 sixty-minute sessions, five times per week, during a period of four weeks. [Results] All participants were evaluated with the Berg Balance Scale, Timed Up and Go (TUG) test, and Activities-specific Balance Confidence (ABC) Scale instrument before and after intervention. After training, the differences in BBS, TUG, and ABC scores in the proprioceptive group were significantly greater than those in the control group. [Conclusion] In conclusion, proprioceptive training was effective on balance ability. Therefore, proprioceptive training may be efficient when combining general physical therapy with phase proprioceptive training for patients with impairments of balance. Further research is needed to investigate proprioceptive training methods.

Design of a case management model for people with chronic disease (Heart Failure and COPD). Phase I: modeling and identification of the main components of the intervention through their actors: patients and professionals (DELTA-icE-PRO Study).

PubMed

Morales-Asencio, Jose M; Martin-Santos, Francisco J; Morilla-Herrera, Juan C; Fernández-Gallego, Magdalena Cuevas; Celdrán-Mañas, Miriam; Navarro-Moya, Francisco J; Rodríguez-Salvador, Maria M; Muñoz-Ronda, Francisco J; Gonzalo-Jiménez, Elena; Carrasco, Almudena Millán

2010-12-02

Chronic diseases account for nearly 60% of deaths around the world. The extent of this silent epidemic has not met determined responses in governments, policies or professionals in order to transform old Health Care Systems, configured for acute diseases. There is a large list of research about alternative models for people with chronic conditions, many of them with an advanced practice nurse as a key provider, as case management. But some methodological concerns raise, above all, the design of the intervention (intensity, frequency, components, etc). General: To develop the first and second phases (theorization and modeling) for designing a multifaceted case-management intervention in people with chronic conditions (COPD and heart failure) and their caregivers. 1) To identify key events in people living with chronic disease and their relation with the Health Care System, from their point of view. 2) To know the coping mechanisms developed by patients and their caregivers along the story with the disease. 3) To know the information processing and its utilization in their interactions with health care providers. 4) To detect potential unmet needs and the ways deployed by patients and their caregivers to resolve them. 5) To obtain a description from patients and caregivers, about their itineraries along the Health Care System, in terms of continuity, accessibility and comprehensiveness of care. 6) To build up a list of promising case-management interventions in patients with Heart Failure and COPD with this information in order to frame it into theoretical models for its reproducibility and conceptualization. 7) To undergo this list to expert judgment to assess its feasibility and pertinence in the Andalusian Health Care. Qualitative research with two phases: For the first five objectives, a qualitative technique with biographic stories will be developed and, for the remaining objectives, an expert consensus through Delphi technique, on the possible interventions yielded from the first phase. The study will be developed in the provinces of Almería, Málaga and Granada in the Southern Spain, from patients included in the Andalusian Health Care Service database with the diagnosis of COPD or Heart Failure, with the collaboration of case manager nurses and general practitioners for the assessment of their suitability to inclusion criteria. Patients and caregivers will be interviewed in their homes or their Health Centers, with their family or their case manager nurse as mediator. First of a series of studies intended to design a case-management service for people with heart failure and COPD, in the Andalusian Health Care System, where case management has been implemented since 2002. Accordingly with the steps of a theoretical model for complex interventions, in this study, theorization and intervention modeling phases will be developed.

GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

ClinicalTrials.gov

2015-12-03

Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

[Epidemiologic and clinical characteristics of patients with hepatitis type C on the bases of selected parameters].

PubMed

Warunek, W; Librant-Suska, M; Krukowiecki, J; Zejc-Bajsarowicz, M; Janas-Skulina, U; Garlicki, A

1996-01-01

We present dates of epidemiological and clinical analysis of patients with chronic hepatitis C. 107 patients were hospitalized in our Chair and Department of Infectious Diseases CM UJ since 1991 till 1995. 41 cases were diagnosed as acute viral hepatitis C and 66 as chronic hepatitis C. In our material 59% cases were nosocomial infections. The certain risk in this group was the surgery (28% of patients). Next possibility of transmission HCV was hospitalization in nonoperative ward (17%). The patients receiving blood or blood products were the next significant risk group of HCV infection. Medical staff is still a certain risk group. About 1/3 of patients have no obvious route of infection. In 70% of patients with hepatitis have the acute phase of HCV infection without any symptoms. 79% cases of acute hepatitis C tends to chronic hepatitis, with high percent of active disease (64%) which can lead after years to cirrhosis or even to hepatocellular carcinoma.

Enhancing mHealth Technology in the Patient-Centered Medical Home Environment to Activate Patients With Type 2 Diabetes: A Multisite Feasibility Study Protocol

PubMed Central

Shi, Lu; Williams, Joel E; Dye, Cheryl J; Chen, Liwei; Crawford, Paul; Shry, Eric A; Griffin, Sarah F; Jones, Karyn O; Sherrill, Windsor W; Truong, Khoa; Little, Jeanette R; Edwards, Karen W; Hing, Marie; Moss, Jennie B

2017-01-01

Background The potential of mHealth technologies in the care of patients with diabetes and other chronic conditions has captured the attention of clinicians and researchers. Efforts to date have incorporated a variety of tools and techniques, including Web-based portals, short message service (SMS) text messaging, remote collection of biometric data, electronic coaching, electronic-based health education, secure email communication between visits, and electronic collection of lifestyle and quality-of-life surveys. Each of these tools, used alone or in combination, have demonstrated varying degrees of effectiveness. Some of the more promising results have been demonstrated using regular collection of biometric devices, SMS text messaging, secure email communication with clinical teams, and regular reporting of quality-of-life variables. In this study, we seek to incorporate several of the most promising mHealth capabilities in a patient-centered medical home (PCMH) workflow. Objective We aim to address underlying technology needs and gaps related to the use of mHealth technology and the activation of patients living with type 2 diabetes. Stated differently, we enable supporting technologies while seeking to influence patient activation and self-care activities. Methods This is a multisite phased study, conducted within the US Military Health System, that includes a user-centered design phase and a PCMH-based feasibility trial. In phase 1, we will assess both patient and provider preferences regarding the enhancement of the enabling technology capabilities for type 2 diabetes chronic care management. Phase 2 research will be a single-blinded 12-month feasibility study that incorporates randomization principles. Phase 2 research will seek to improve patient activation and self-care activities through the use of the Mobile Health Care Environment with tailored behavioral messaging. The primary outcome measure is the Patient Activation Measure scores. Secondary outcome measures are Summary of Diabetes Self-care Activities Measure scores, clinical measures, comorbid conditions, health services resource consumption, and technology system usage statistics. Results We have completed phase 1 data collection. Formal analysis of phase 1 data has not been completed. We have obtained institutional review board approval and began phase 1 research in late fall 2016. Conclusions The study hypotheses suggest that patients can, and will, improve their activation in chronic care management. Improved activation should translate into improved diabetes self-care. Expected benefits of this research to the scientific community and health care services include improved understanding of how to leverage mHealth technology to activate patients living with type 2 diabetes in self-management behaviors. The research will shed light on implementation strategies in integrating mHealth into the clinical workflow of the PCMH setting. Trial Registration ClinicalTrials.gov NCT02949037. https://clinicaltrials.gov/ct2/show/NCT02949037. (Archived by WebCite at http://www.webcitation.org/6oRyDzqei) PMID:28264792

Can chronic myeloid leukaemia in children and adolescents be successfully treated without haematopoietic stem cell transplant? A single centre experience.

PubMed

Giona, Fiorina; Moleti, Maria L; De Benedittis, Daniela; Santopietro, Michelina; Nanni, Mauro; Testi, Anna M; Orlando, Sonia; Iori, Anna P; Piciocchi, Alfonso; Gottardi, Enrico; Barberi, Walter; Diverio, Daniela; Saglio, Giuseppe; Foà, Robin

2016-06-01

We analysed the long-term outcome of 35 children and adolescents (<20 years at diagnosis) with chronic myeloid leukaemia (CML) in chronic phase: 20 patients had received interferon-alpha and/or tyrosine kinase inhibitors (TKIs), and 15 underwent a haematopoietic stem cell transplant. The 10-year survival probabilities were similar in transplanted and non-transplanted patients (73·3% vs. 72·1%, respectively), whereas the survival probability was significantly lower in patients diagnosed before 1999 compared to those diagnosed afterwards (62·1% vs. 100%, P = 0·0384). The availability of TKIs and the standardized molecular monitoring have significantly improved treatment, management and outcome in children and adolescents with CML. © 2016 John Wiley & Sons Ltd.

Oral Rehabilitation of a Severe Periodontally Involved Patient with Mucous Membrane Pemphigoid: A 15-Year Follow-Up Case Report.

PubMed

Megarbane, Jean-Marie; Freiha, Cécile; Mokbel, Nadim

Mucous membrane pemphigoid (MMP) refers to a group of chronic autoimmune subepithelial diseases distinguished by erosive lesions of the mucous membranes and skin. Its treatment consists of inhibition of the inflammatory reaction by means of corticosteroids and symptomatic medication. This is a report of a patient suffering from a combination of MMP and severe generalized chronic periodontitis. The patient has been treated with oral corticosteroids, initial phase therapy, extraction with immediate implant placement, and periodontal surgery where the prognosis was questionable. The case has been followed up for 15 years. Periodontal therapy with immediate implant placement was determined to be a viable modality to achieve a total rehabilitation of a case suffering from MMP combined with severe generalized chronic periodontitis.

Diagnosis of Chagas' cardiomyopathy. Non-invasive techniques.

PubMed Central

Puigbó, J. J.; Valecillos, R.; Hirschhaut, E.; Giordano, H.; Boccalandro, I.; Suárez, C.; Aparicio, J. M.

1977-01-01

The natural history of Chagas' disease and its manifestations when the heart is involved are detailed clinically and pathologically. Three phases are recognized: the acute phase, lasting from 1-3 months, the latent phase, which may last from 10-20 years, and the chronic phase, which has the most serious manifestations. This phase is subdivided into three clinical stages. An analysis of the varied cardiac manifestations on 235 patients is included. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:412174

Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Blood Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

ClinicalTrials.gov

2017-10-30

Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B-Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma

Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.

PubMed

Shashaty, George; Frankewich, Raymond; Chakraborti, Tamal; Choudary, Jasti; Al-Fayoumi, Suliman; Kacuba, Alice; Castillo, Sonia; Robie-Suh, Kathy; Rieves, Dwaine; Weiss, Karen; Pazdur, Richard

2006-12-01

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis. The FDA reviewed findings of a controlled, open-label, randomized multicenter phase III study of deferasirox vs. deferoxamine in 586 patients with beta-thalessemia and transfusional hemosiderosis. The study results as well as the results of the FDA review of chemistry, preclinical pharmacology, and supportive studies are described. Following 48 weeks of treatment in the phase III study, patients' liver iron concentrations (a key endpoint variable) had decreased an average of 2.4 mg of iron (Fe)/g dry weight (dw) and 2.9 mg Fe/g dw in the deferasirox and deferoxamine groups, respectively, despite continued blood transfusions in both cohorts. Deferasirox was associated with serum creatinine increases in approximately a third of patients. Common adverse events included gastrointestinal symptoms and skin rash. Other data provided supportive evidence of deferasirox safety and efficacy. The FDA granted deferasirox accelerated approval on November 2, 2005, for use in treating chronic iron overload due to transfusional hemosiderosis in patients > or =2 years of age. The sponsor must obtain clinical data demonstrating the drug's long-term safety and effectiveness.

Current approach to the treatment of chronic myeloid leukaemia.

PubMed

Pasic, Ivan; Lipton, Jeffrey H

2017-04-01

Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP). Copyright © 2017 Elsevier Ltd. All rights reserved.

Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia

PubMed Central

Heller, G; Topakian, T; Altenberger, C; Cerny-Reiterer, S; Herndlhofer, S; Ziegler, B; Datlinger, P; Byrgazov, K; Bock, C; Mannhalter, C; Hörmann, G; Sperr, W R; Lion, T; Zielinski, C C; Valent, P; Zöchbauer-Müller, S

2016-01-01

Little is known about the impact of DNA methylation on the evolution/progression of Ph+ chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. Although only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared with controls, ~6500 differentially methylated CpG sites were found in samples from BC-CML patients. In the majority of affected CpG sites, methylation was increased. In CP-CML patients who progressed to AP-CML/BC-CML, we identified up to 897 genes that were methylated at the time of progression but not at the time of diagnosis. Using RNA-sequencing, we observed downregulated expression of many of these genes in BC-CML compared with CP-CML samples. Several of them are well-known tumor-suppressor genes or regulators of cell proliferation, and gene re-expression was observed by the use of epigenetic active drugs. Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML. PMID:27211271

Bochum ultrasound score versus clinical and electrophysiological parameters in distinguishing acute-onset chronic from acute inflammatory demyelinating polyneuropathy.

PubMed

Kerasnoudis, Antonios; Pitarokoili, Kallia; Behrendt, Volker; Gold, Ralf; Yoon, Min-Suk

2015-06-01

The aim of this study was to evaluate whether a nerve ultrasound score (Bochum ultrasound score, BUS), clinical, and electrophysiological parameters could distinguish subacute chronic (CIDP) from acute inflammatory demyelinating polyneuropathy (AIDP). Phase 1: The charts of 35 patients with polyradiculoneuropathy were evaluated retrospectively regarding BUS, clinical, and electrophysiological parameters (A-waves, sural nerve sparing pattern, sensory ratio>1). Phase 2: All parameters were evaluated prospectively in 10 patients with subacute polyradiculoneuropathy. Phase 1: A sum score of ≥2 points in BUS and the presence of sensory symptoms were significantly more frequent in the subacute CIDP group than in the AIDP group (P<0.001).The electrophysiological parameters showed no significant changes between the 2 groups. Phase 2: BUS (83.3%; 100%;), sensory symptoms (100%; 75%), absence of autonomic nervous system dysfunction (83.3%; 75%), or bulbar palsy (83.3%; 50%) showed the best sensitivity and specificity in distinguishing subacute CIDP from AIDP. BUS is a useful diagnostic tool for distinguishing subacute CIDP from AIDP. © 2014 Wiley Periodicals, Inc.

Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

ClinicalTrials.gov

2014-12-22

Accelerated Phase of Disease; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: a Chinese perspective study.

PubMed

Zeng, Lin-Yan; Lian, Jiang-Shan; Chen, Jian-Yang; Jia, Hong-Yu; Zhang, Yi-Min; Xiang, Dai-Rong; Yu, Liang; Hu, Jian-Hua; Lu, Ying-Feng; Zheng, Lin; Li, Lan-Juan; Yang, Yi-Da

2014-07-21

To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China. Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined. Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log10 IU/mL), IC (4.36 log10 IU/mL), ENH (2.95 log10 IU/mL), LR (3.18 log10 IU/mL) and LC (2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed. The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy.

Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia.

PubMed

Elmaagacli, Ahmet H; Basoglu, Semiha; Peceny, Rudolf; Trenschel, Rudolf; Ottinger, Hellmut; Lollert, Andre; Runde, Volker; Grosse-Wilde, Hans; Beelen, Dietrich W; Schaefer, Ulrich W

2002-02-15

Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was associated with improved immune reconstitution, with higher peripheral blood naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months and 12 months after transplantation (P <.03). The cumulative incidence of acute (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT was associated with a higher cumulative incidence of severe, acute (grade III-IV) GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4-week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not significant). Seventeen of the 54 patients died after BMT (31%), as compared with 2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly with infections and severe, acute GVHD. The estimated probability of transplant-related mortality (TRM) and disease-free survival at 1000 days after receiving the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT group (P <.03). Overall survival 1000 days after receiving the transplant was 66% after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute GVHD significantly influenced TRM (P <.01).

Periodic limb movements during sleep in stroke/TIA: Prevalence, course, and cardiovascular burden.

PubMed

Manconi, Mauro; Fanfulla, Francesco; Ferri, Raffaele; Miano, Silvia; Haba-Rubio, Josè; Heinzer, Raphael; Horvath, Thomas; Proserpio, Paola; Young, Peter; Moschovitis, Giorgio; Seiler, Andrea; Cereda, Carlo; Nobili, Lino; Wiest, Roland; Ott, Sebastian R; Bassetti, Claudio L

2018-05-08

To define the prevalence, time course, and associated factors of periodic limb movements during sleep (PLMS) in patients with ischemic stroke or TIA. Patients enrolled in the prospective Sleep-Disordered Breathing in Transient Ischemia Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy (SAS-CARE) study underwent a double polysomnographic investigation in the acute and chronic phases after stroke/TIA, together with a MRI brain scan and a 24-hour blood pressure evaluation. The prevalence of PLMS in patients was compared with that in a matched sample of randomly selected healthy controls from the HypnoLaus cohort. One hundred sixty-nine recordings were performed in the acute phase and 191 after 3 months (210 recordings were obtained from the same 105 patients in both phases) and were compared to those of 162 controls. The mean number of PLMS per hour and the percentage of participants with a PLMS index >10 and >15 per hour were similar between patients and controls. PLMS remained stable from the acute to the chronic phase after stroke. Factors positively associated with PLMS were age, body mass index, and history of hypertension. Blood pressure over 24 hours and the burden of cerebrovascular damage were similar between the groups with PLMS and without PLMS. PLMS are equally frequent in patients with stroke/TIA and the general population. The absence of higher blood pressure values and of a greater vascular brain damage found in patients with PLMS compared to those without PLMS might be due to a greater use of antihypertensive medication among patients with PLMS, which corresponds to a higher prevalence of previous diagnosis of hypertension in these patients. © 2018 American Academy of Neurology.

Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era-experience from a tertiary oncology centre in Southern India.

PubMed

Kuntegowdanahalli, Lakshmaiah Chinnagiriyappa; Kanakasetty, Govind Babu; Thanky, Aditi Harsh; Dasappa, Lokanatha; Jacob, Linu Abraham; Mallekavu, Suresh Babu; Lakkavalli, Rajeev Krishnappa; Kadabur, Lokesh N; Haleshappa, Rudresha Antapura

2016-01-01

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.

Arthroscopic excision of heterotopic calcification in a chronic rectus femoris origin injury: a case report

PubMed Central

El-Husseiny, M; Sukeik, M; Haddad, FS

2012-01-01

Rectus femoris origin injuries in adult athletes are uncommon. In the acute phase, conservative treatment seems to have a favourable outcome, with surgical repair reserved for unsuccessful cases only. However, a group of patients may develop chronic pain and disability after recovery from the acute phase due to heterotopic calcification occurring at the site of injury. Open and arthroscopic excision of such calcifications has been described in the literature although arthroscopic excision of large calcified lesions in the rectus femoris has not been reported previously. A relevant case is presented and discussed. PMID:22507710

Amplification of the BCR/ABL fusion gene clustered on a masked Philadelphia chromosome in a patient with myeloblastic crisis of chronic myelocytic leukemia.

PubMed

Gargallo, Patricia M; Cuello, Maria Teresa; Aranguren, Pedro Negri; Larripa, Irene B

2003-06-01

Although the chronic phase of chronic myelocytic leukemia (CML) is characterized by the Philadelphia (Ph) chromosome creating a hybrid BCR/ABL gene, additional genetic changes involved in blast crisis are poorly understood. We report a 4-8-fold amplification by tandem duplication of the BCR/ABL fusion gene clustered on a masked Ph chromosome in a 61-year-old male patient with CML in myeloblastic crisis. Our finding suggests that the BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Ph-positive CML.

Prognostic discrimination for early chronic phase chronic myeloid leukemia in imatinib era: comparison of Sokal, Euro, and EUTOS scores in Korean population.

PubMed

Yahng, Seung-Ah; Jang, Eun-Jung; Choi, Soo-Young; Lee, Sung-Eun; Kim, Soo-Hyun; Kim, Dong-Wook

2014-08-01

Beyond the conventional Sokal and Euro scores, a new prognostic risk classification, based on the European Treatment Outcome Study (EUTOS), has been developed to predict the outcome of treatment with tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML). In the present study, each risk score was validated by various endpoints in 206 Korean patients with early chronic-phase CML treated with up-front standard dose imatinib. In our analysis, all three scores were found to be valid. The 5-year event-free survival (EFS) was significantly discriminated using Sokal (P = 0.002), Euro (P = 0.003), and EUTOS (P = 0.029), with the worst probability by Euro high-risk (62 vs. 49 vs. 67 %) and better EFS in Sokal low-risk (89 vs. 86 vs. 82 %). Combining all scores identified 6 % of all patients having homogeneous high-risk with distinctively worse outcomes (5-year EFS of 41 %, cumulative complete cytogenetic response rate of 56 %, and cumulative major molecular response rate of 27 %), whereas the group of discordance in risk scores (60 %) had similar results to those of intermediate-risk groups of Sokal and Euro scores. Combining all risk scores for baseline risk assessment may be useful in clinical practice for identifying groups of patients who may benefit from treatment initiation with a more potent TKI among the currently available first-line TKIs.

A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia

PubMed Central

Dale, David C.; Bonilla, Mary Ann; Davis, Mark W.; Nakanishi, Arline M.; Hammond, William P.; Kurtzberg, Joanne; Wang, Winfred; Jakubowski, Ann; Winton, Elliott; Lalezari, Parviz; Robinson, William; Glaspy, John A.; Emerson, Steve; Gabrilove, Janice; Vincent, Martha; Boxer, Laurence A.

2014-01-01

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 × 109/L) due to these diseases were enrolled in this multi-center phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 μg/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of ≥ 1.5 × 109/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently: adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. PMID:8490166

[Experience in treating patients with chronic obstructive bronchitis with fenspirid].

PubMed

Kirichenko, A A; Shabanova, T M

2002-01-01

To study a clinical effect of fenspirid and its impact on external respiration function in patients with chronic obstructive bronchitis (COB) in the exacerbation phase. 30 COB patients participated in the trial (20 males, 10 females, age 39-80 years). The severity of clinical symptoms (cough, sputum, dyspnea) was studied using special scales. External respiration function was examined by a spirometric system "Tamrac system spiro sense Y2 14". Fenspirid treatment was conducted in a dose 80 mg twice a day for 3 months. Control examinations were made 2 weeks, 1 and 3 months after the treatment start. A 3-month treatment with fenspirid resulted in regression of COB symptoms: cough and sputum ceased, dyspnea decreased. This led to improvement in external respiration function, especially in patients with mixed ventilatory disorders with prevailing restriction. Fenspirid is an effective and well tolerated treatment of chronic obstructive bronchitis.

Perceived Barriers and Support Strategies for Reducing Sodium Intake in Patients with Chronic Kidney Disease: a Qualitative Study.

PubMed

Meuleman, Yvette; Ten Brinke, Lucia; Kwakernaak, Arjan J; Vogt, Liffert; Rotmans, Joris I; Bos, Willem Jan W; van der Boog, Paul J M; Navis, Gerjan; van Montfrans, Gert A; Hoekstra, Tiny; Dekker, Friedo W; van Dijk, Sandra

2015-08-01

Reducing sodium intake can prevent cardiovascular complications and further decline of kidney function in patients with chronic kidney disease. However, the vast majority of patients fail to reach an adequate sodium intake, and little is known about why they do not succeed. This study aims to identify perceived barriers and support strategies for reducing sodium intake among both patients with chronic kidney disease and health-care professionals. A purposive sample of 25 patients and 23 health-care professionals from 4 Dutch medical centers attended 8 focus groups. Transcripts were analyzed thematically and afterwards organized according to the phases of behavior change of self-regulation theory. Multiple themes emerged across different phases of behavior change, including the patients' lack of practical knowledge and intrinsic motivation, the maladaptive illness perceptions and refusal skills, the lack of social support and feedback regarding disease progression and sodium intake, and the availability of low-sodium foods. The results indicate the need for the implementation of support strategies that target specific needs of patients across the whole process of changing and maintaining a low-sodium diet. Special attention should be paid to supporting patients to set sodium-related goals, strengthening intrinsic motivation, providing comprehensive and practical information (e.g., about hidden salt in products), increasing social support, stimulating the self-monitoring of sodium intake and disease progression, and building a supportive patient-professional relationship that encompasses shared decision making and coaching. Moreover, global programs should be implemented to reduce sodium levels in processed foods, introduce sodium-related product labels, and increase consumer awareness.

Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

ClinicalTrials.gov

2013-09-27

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia.

PubMed

Choi, Michael Y; Widhopf, George F; Ghia, Emanuela M; Kidwell, Reilly L; Hasan, Md Kamrul; Yu, Jian; Rassenti, Laura Z; Chen, Liguang; Chen, Yun; Pittman, Emily; Pu, Minya; Messer, Karen; Prussak, Charles E; Castro, Januario E; Jamieson, Catriona; Kipps, Thomas J

2018-06-01

Cirmtuzumab is a humanized monoclonal antibody (mAb) that targets ROR1, an oncoembryonic orphan receptor for Wnt5a found on cancer stem cells (CSCs). Aberrant expression of ROR1 is seen in many malignancies and has been linked to Rho-GTPase activation and cancer stem cell self-renewal. For patients with chronic lymphocytic leukemia (CLL), self-renewing, neoplastic B cells express ROR1 in 95% of cases. High-level leukemia cell expression of ROR1 is associated with an unfavorable prognosis. We conducted a phase 1 study involving 26 patients with progressive, relapsed, or refractory CLL. Patients received four biweekly infusions, with doses ranging from 0.015 to 20 mg/kg. Cirmtuzumab had a long plasma half-life and did not have dose-limiting toxicity. Inhibition of ROR1 signaling was observed, including decreased activation of RhoA and HS1. Transcriptome analyses showed that therapy inhibited CLL stemness gene expression signatures in vivo. Cirmtuzumab is safe and effective at inhibiting tumor cell ROR1 signaling in patients with CLL. Copyright © 2018. Published by Elsevier Inc.

Influence of oral health condition on swallowing and oral intake level for patients affected by chronic stroke.

PubMed

Mituuti, Cláudia T; Bianco, Vinicius C; Bentim, Cláudia G; de Andrade, Eduardo C; Rubo, José H; Berretin-Felix, Giédre

2015-01-01

According to the literature, the occurrence of dysphagia is high in cases of stroke, and its severity can be enhanced by loss of teeth and the use of poorly fitting prostheses. To verify that the status of oral health influences the level of oral intake and the degree of swallowing dysfunction in elderly patients with stroke in chronic phase. Thirty elderly individuals affected by stroke in chronic phase participated. All subjects underwent assessment of their oral condition, with classification from the Functional Oral Intake Scale (FOIS) and nasoendoscopic swallowing assessment to classify the degree of dysphagia. The statistical analysis examined a heterogeneous group (HG, n=30) and two groups designated by the affected body part, right (RHG, n=8) and left (LHG, n=11), excluding totally dentate or edentulous individuals without rehabilitation with more than one episode of stroke. There was a negative correlation between the need for replacement prostheses and the FOIS scale for the HG (P=0.02) and RHG (P=0.01). Differences in FOIS between types of prostheses of the upper dental arch in the LHG (P=0.01) and lower dental arch in the RHG (P=0.04). A negative correlation was found between the number of teeth present and the degree of dysfunction in swallowing liquid in the LHG (P=0.05). There were differences in the performance in swallowing solids between individuals without prosthesis and those with partial prosthesis in the inferior dental arch (P=0.04) for the HG. The need for replacement prostheses, type of prostheses, and the number of teeth of elderly patients poststroke in chronic phase showed an association with the level of oral intake and the degree of oropharyngeal dysphagia.

In search of attachment: a qualitative study of chronically ill women transitioning between family physicians in rural Ontario, Canada.

PubMed

Randall, Ellen; Crooks, Valorie A; Goldsmith, Laurie J

2012-12-23

Most Canadians receive basic health services from a family physician and these physicians are particularly critical in the management of chronic disease. Canada, however, has an endemic shortage of family physicians. Physician shortages and turnover are particularly acute in rural regions, leaving their residents at risk of needing to transition between family physicians. The knowledge base about how patients manage transitioning in a climate of scarcity remains nascent. The purpose of this study is to explore the experience of transitioning for chronically ill, rurally situated Canadian women to provide insight into if and how the system supports transitioning patients and to identify opportunities for enhancing that support. Chronically ill women managing rheumatic diseases residing in two rural counties in the province of Ontario were recruited to participate in face-to-face, semi-structured interviews. Interview transcripts were analysed thematically to identify emergent themes associated with the transitioning experience. Seventeen women participated in this study. Ten had experienced transitioning and four with long-standing family physicians anticipated doing so soon. The remaining three expressed concerns about transitioning. Thematic analysis revealed the presence of a transitioning trajectory with three phases. The detachment phase focused on activities related to the termination of a physician-patient relationship, including haphazard notification tactics and the absence of referrals to replacement physicians. For those unable to immediately find a new doctor, there was a phase of unattachment during which patients had to improvise ways to receive care from alternative providers or walk-in clinics. The final phase, attachment, was characterized by acceptance into the practice of a new family physician. Participants often found transitioning challenging, largely due to perceived gaps in support from the health care system. Barriers to a smooth transition included inadequate notification procedures, lack of formal assistance finding new physicians, and unsatisfactory experiences seeking care during unattachment. The participants' accounts reveal opportunities for a stronger system presence during transition and a need for further research into alternative models of primary care delivery.

Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

PubMed

Hill, Nicholas S; Rahaghi, Franck F; Sood, Namita; Frey, Reiner; Ghofrani, Hossein-Ardeschir

2017-08-01

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A.

PubMed

Cho, Hyosun; Kang, Hyojeung; Kim, Chang Wook; Kim, Hee Yeon; Jang, Jeong Won; Yoon, Seung Kew; Lee, Chang Don

2016-03-01

The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.

[Star fruit (Averrhoa carambola) toxic encephalopathy].

PubMed

Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D

2009-03-01

Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.

Transitions of Care Between Acute and Chronic Heart Failure: Critical Steps in the Design of a Multidisciplinary Care Model for the Prevention of Rehospitalization.

PubMed

Comín-Colet, Josep; Enjuanes, Cristina; Lupón, Josep; Cainzos-Achirica, Miguel; Badosa, Neus; Verdú, José María

2016-10-01

Despite advances in the treatment of heart failure, mortality, the number of readmissions, and their associated health care costs are very high. Heart failure care models inspired by the chronic care model, also known as heart failure programs or heart failure units, have shown clinical benefits in high-risk patients. However, while traditional heart failure units have focused on patients detected in the outpatient phase, the increasing pressure from hospital admissions is shifting the focus of interest toward multidisciplinary programs that concentrate on transitions of care, particularly between the acute phase and the postdischarge phase. These new integrated care models for heart failure revolve around interventions at the time of transitions of care. They are multidisciplinary and patient-centered, designed to ensure continuity of care, and have been demonstrated to reduce potentially avoidable hospital admissions. Key components of these models are early intervention during the inpatient phase, discharge planning, early postdischarge review and structured follow-up, advanced transition planning, and the involvement of physicians and nurses specialized in heart failure. It is hoped that such models will be progressively implemented across the country. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Self-Management: Enabling and empowering patients living with cancer as a chronic illness

PubMed Central

McCorkle, Ruth; Ercolano, Elizabeth; Lazenby, Mark; Schulman-Green, Dena; Schilling, Lynne S.; Lorig, Kate; Wagner, Edward H.

2010-01-01

With recent improvements in early detection, diagnosis and treatment of cancer, people with cancer are living longer, and their cancer may be managed as a chronic illness. Cancer as a chronic illness places new demands on patients and families to manage their own care, and it challenges old paradigms that oncology's work is done after treatment. As a chronic illness, however, cancer care occurs on a continuum that stretches from prevention to the end of life, with early detection, diagnosis, treatment, and survivorship in between. In this paper, we review self-management interventions that enable patients and families to participate in managing their care along this continuum. We review randomized controlled trials of self-management interventions with cancer patients and families in the treatment, survivorship, and end-of-life phases of the cancer-care continuum. We also present the Chronic Care Model as a model of care that oncology practices can use to enable and empower patients and families to engage in self-management. We conclude that, the need for a common language by which to speak about self-management and a common set of self-management actions for cancer care notwithstanding, oncology practices can now build strong relationships with their patients and formulate mutually-agreed upon care plans that enable and empower patients to care for themselves in the way they prefer. PMID:21205833

Rationale and motivating factors for treatment-free remission in chronic myeloid leukemia.

PubMed

Caldemeyer, Lauren; Akard, Luke P

2016-12-01

With BCR-ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, many patients with chronic myeloid leukemia in chronic phase (CML-CP) can expect to live near-normal life spans. Current treatment recommendations of the National Comprehensive Cancer Network and the European LeukemiaNet state that patients with CML-CP should remain on TKI therapy indefinitely. However, there is increasing evidence from clinical trials that some patients with sustained deep molecular responses may be able to achieve treatment-free remission (TFR), whereby they can suspend TKI therapy without losing previously achieved responses. With many patients achieving deep molecular responses to TKI therapy, there is growing interest in whether such patients can achieve TFR. In addition, adverse events (AEs) with long-term TKI therapy, including both the potential for later-emerging AEs and chronic, low-grade AEs, represent a major motivator for oncologists and their patients to investigate the feasibility of TFR. In this review, we provide an overview of data from TFR clinical trials, discuss the importance of achieving a deep molecular response to TKI treatment, and consider potential reasons for investigating TFR following TKI therapy.

Self-management support in chronic illness care: a concept analysis.

PubMed

Kawi, Jennifer

2012-01-01

This article reports on the concept analysis of self-management support (SMS) to provide clarity for systematic implementation in practice. SMS is a concept in its early phase of development. It is increasingly evident in literature on chronic illness care. However, the definition has been simplified or vague leading to variable SMS programs and inconsistent outcomes. Elucidation of SMS is necessary in chronic illness care to facilitate clear understanding and implementation. Rodgers' evolutionary concept analysis method was used to examine SMS. Data sources included systematic multidisciplinary searches of multiple search engines. SMS refers to comprehensive sustaining approaches toward improving chronic illness outcomes consisting of patient-centered attributes (involving patients as partners; providing diverse, innovative educational modalities specific to patients' needs; individualizing patient care), provider attributes (possessing adequate knowledge, skills, attitudes in providing care), and organizational attributes (putting an organized system of care in place, having multidisciplinary team approach, using tangible and social support). A well-clarified SMS concept is important in theory development. The attributes offer necessary components in SMS programs for systematic implementation, evaluation, and research. There is great potential that SMS can help improve outcomes of chronic illness care.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wasser, M.N.; Schultze Kool, L.J.; Roos, A. de

Our goal was to assess the value of MRA for detecting stenoses in the celiac (CA) and superior mesenteric (SMA) arteries in patients suspected of having chronic mesenteric ischemia, using an optimized systolically gated 3D phase contrast technique. In an initial study in 24 patients who underwent conventional angiography of the abdominal vessels for different clinical indications, a 3D phase contrast MRA technique (3D-PCA) was evaluated and optimized to image the CAs and SMAs. Subsequently, a prospective study was performed to assess the value of systolically gated 3D-PCA in evaluation of the mesenteric arteries in 10 patients with signs andmore » symptoms of chronic mesenteric ischemia. Intraarterial digital subtraction angiography and surgical findings were used as the reference standard. In the initial study, systolic gating appeared to be essential in imaging the SMA on 3D-PCA. In 10 patients suspected of mesenteric ischemia, systolically gated 3D-PCA identified significant proximal disease in the two mesenteric vessels in 4 patients. These patients underwent successful reconstruction of their stenotic vessels. Cardiac-gated MRA may become a useful tool in selection of patients suspected of having mesenteric ischemia who may benefit from surgery. 16 refs., 6 figs., 4 tabs.« less

Correlation between preferentially expressed antigen of melanoma and tumour necrosis factor-related apoptosis-inducing ligand gene expression in different types of leukaemia patients.

PubMed

Zhang, Wenhui; Chi, Kaikai; Zhang, Yin; Ma, Baogen; Shi, Jie; Chen, Yuqing; Lei, Pingchong; Li, Yulong; Sun, Kai

2013-01-01

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) down-regulation by preferentially expressed antigen of melanoma (PRAME) is a general phenomenon in different types of solid tumours, but research on the correlation between PRAME and TRAIL gene expression in leukaemia patients is rare. PRAME and TRAIL expression was detected in bone marrow samples from 80 newly diagnosed acute leukaemia (AL) patients and 40 chronic myeloid leukaemia (CML) patients using TaqMan-based real-time quantitative PCR methods, and a linear correlation analysis was performed on their levels of expression. A total of 15 normal bone marrow samples from individuals with non-malignant haematological diseases served as normal controls. PRAME expression was higher in both AL and CML patients compared to controls (both p < 0.001). CML patients in both blast crisis (BC) and the accelerated phase (AP) had significantly higher PRAME levels than CML patients in the chronic phase (CP) (p = 0.006 and 0.0461, respectively). TRAIL expression was higher in both the acute myeloid leukaemia (AML) group and the acute lymphoblastic leukaemia (ALL) group than in the controls (p = 0.039 and 0.047, respectively). In contrast, CML patients had lower TRAIL levels than controls (p = 0.043), and TRAIL expression in CML patients in the advanced phases (BC and AP) was significantly lower than in CML-CP patients (p = 0.006). In CML patients, there was a significant inverse correlation (Spearman's R = -0.6669, p < 0.0001) between PRAME and TRAIL gene expression, while a greater significant inverse correlation was found in patients in the advanced phases (BC and AP) (R = -0.6764). In addition, no correlation was observed in AML and ALL patients. The simultaneous detection of PRAME and TRAIL gene expression may be helpful to monitor condition changes in leukaemia patients and evaluate therapeutic effects in clinical practice, particularly in CML patients. © 2013 S. Karger AG, Basel.

Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.

PubMed

Bruchfeld, Annette; Roth, David; Martin, Paul; Nelson, David R; Pol, Stanislas; Londoño, Maria-Carlota; Monsour, Howard; Silva, Marcelo; Hwang, Peggy; Arduino, Jean-Marie; Robertson, Michael; Nguyen, Bach-Yen; Wahl, Janice; Barr, Eliav; Greaves, Wayne

2017-08-01

In the C-SURFER study, therapy with the all-oral elbasvir plus grazoprevir regimen for 12 weeks in patients with chronic hepatitis C virus (HCV) infection and stage 4-5 chronic kidney disease resulted in a high rate of virological cure compared with placebo. Here, we report sustained virological response (SVR), safety data, health-related quality-of-life (HRQOL), and virological resistance analyses in patients in C-SURFER who received immediate antiviral therapy or who received placebo before therapy. In this phase 3, multicentre, randomised, placebo-controlled study, we randomly assigned adults with HCV genotype 1 infection and stage 4-5 chronic kidney disease enrolled at 68 centres worldwide to either elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks (immediate treatment group) or placebo for 12 weeks followed by elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks beginning at week 16 (deferred treatment group). The primary safety and efficacy endpoints for the immediate treatment group and placebo phase of the deferred treatment group have been reported previously. Here, we report safety and efficacy data for the treatment phase of the deferred treatment group, as well as HRQOL assessed using the 36-Item Short Form Health Survey for all groups, and baseline and treatment-emergent resistance-associated substitutions (RASs). SVR at 12 weeks (SVR12) was assessed in the modified full analysis set (FAS), defined as all patients excluding those who did not receive at least one dose of study drug, who died, or who discontinued the study before the end of treatment for reasons determined to be unrelated to HCV treatment. This trial is registered with ClinicalTrials.gov, Number NCT02092350. Between March 30 and Nov 28, 2014, 235 patients were enrolled and received at least one dose of study drug. The modified FAS included 116 patients assigned to immediate treatment and 99 assigned to deferred treatment. 115 (99·1%; 95% CI 95·3-100·0) of 116 assigned to immediate treatment achieved SVR12 compared with 97 (98·0%; 92·9-99·7) of 99 assigned to deferred treatment. In patients with genotype 1a infections, SVR12 was achieved by 11 (84·6%) of 13 patients with detectable baseline NS5A RASs and in 98 (100%) of 98 without. HRQOL did not differ at week 12 between immediate treatment and the placebo phase of deferred treatment. Safety was generally similar between patients receiving immediate treatment and those receiving placebo in the deferred treatment group. One serious adverse event during deferred treatment (interstitial nephritis) and one during the placebo phase of deferred treatment (raised lipase concentration) were deemed related to study drug. Four patients died, one who received immediate treatment (cardiac arrest) and three who received deferred treatment (aortic aneurysm, pneumonia, and unknown cause); all four deaths were considered unrelated to study drugs. Of the three deaths in the deferred treatment group, one occurred during placebo treatment and two occurred before starting active treatment. There were no notable differences in aminotransferase elevations in the deferred treatment group compared with the immediate treatment group, and no patients in the deferred treatment group had total bilirubin elevations. These data add to the growing body of clinical evidence for the fixed-dose combination regimen of elbasvir plus grazoprevir for 12 weeks and support use of this therapy in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. Merck Sharp & Dohme. Copyright © 2017 Elsevier Ltd. All rights reserved.

Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials.

PubMed

Locatelli, Francesco; Choukroun, Gabriel; Truman, Matt; Wiggenhauser, Alfons; Fliser, Danilo

2016-04-01

Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups. Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (<65/≥65), baseline N-terminal pro-B-type natriuretic peptide levels (<5000/≥5000), cardiovascular risk factors (diabetes/cardiac/vascular/none). Across all subgroups analyzed, switching from shorter-acting erythropoiesis-stimulating agents to continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin concentrations in a high proportion of patients (78%), with only moderate hemoglobin fluctuations and a low number of dose changes. The safety profile across subgroups was as expected based on pre-existing risk factors; observed increases in adverse events were attributable to underlying risk factors rather than study drug. This retrospective analysis of 13 trials showed that continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin levels across a number of clinically relevant patient subgroups, including those with higher inherent cardiovascular risk. The safety profile was consistent with that previously established in the chronic kidney disease population. CLINICALTRIALS. NCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348. F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Developmental Therapeutics Consortium report on study design effects on trial outcomes in chronic myeloid leukaemia.

PubMed

Giles, Francis; Mahon, François-Xavier; Gjertsen, Bjorn; Swords, Ronan; Labar, Boris; Turkina, Anna; Rosti, Gianantonio

2012-09-01

Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukaemia (CML). Results from ongoing phase 3 trials with nilotinib [Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd)] and dasatinib [Dasatinib Versus Imatinib Study in Treatment-Naive CML-CP Patients (DASISION)] in newly diagnosed patients with CML in chronic phase have demonstrated that these TKIs resulted in significant improvements in responses vs. imatinib. The Developmental Therapeutics Consortium (DTC) systematically reviewed the published literature to provide a comparative analysis of the ENESTnd and DASISION trial designs and data reported on each study. The recent approval of nilotinib and dasatinib based on these two pivotal studies offers physicians the option to optimise frontline treatment based on a patient's comorbidities, risk factors and tolerability profiles. Although nilotinib and dasatinib provide effective therapeutic options for the frontline treatment of CML, the lack of an evidenced-based, side-by-side comparison makes it difficult to directly compare these agents. Despite potential bias from differences in patient populations and study design, indirect cross-trial comparisons to determine the relative effectiveness of these agents will be performed by physicians. This DTC report provides a comprehensive summary of the study designs, protocols and results of the ENESTnd and DASISION trials, which will assist physicians in making informed decisions on the best treatment approach for their patients. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury.

PubMed

Hattori, Naoya; Swan, Megan; Stobbe, Gary A; Uomoto, Jay M; Minoshima, Satoshi; Djang, David; Krishnananthan, Ruben; Lewis, David H

2009-07-01

Patients with mild traumatic brain injury (TBI) often complain of cognitive fatigue during the chronic recovery phase. The Paced Auditory Serial Addition Test (PASAT) is a complex psychologic measure that may demonstrate subtle deficiencies in higher cognitive functions. The purpose of this study was to investigate the brain activation of regional cerebral blood flow (rCBF) with PASAT in patients with mild TBI to explore mechanisms for the cognitive fatigue. Two groups consisting of 15 patients with mild TBI and 15 healthy control subjects underwent (99m)Tc-ethylene cysteine dimer SPECT at rest and during PASAT on a separate day. Cortical rCBF was extracted using a 3-dimensional stereotactic surface projection and statistically analyzed to identify areas of activation, which were compared with PASAT performance scores. Image analysis demonstrated a difference in the pattern of activation between patients with mild TBI and healthy control subjects. Healthy control subjects activated the superior temporal cortex (Brodmann area [BA] 22) bilaterally, the precentral gyrus (BA 9) on the left, and the precentral gyrus (BA 6) and cerebellum bilaterally. Patients with mild TBI demonstrated a larger area of supratentorial activation (BAs 9, 10, 13, and 46) but a smaller area of activation in the cerebellum, indicating frontocerebellar dissociation. Patients with mild TBI and cognitive fatigue demonstrated a different pattern of activation during PASAT. Frontocerebellar dissociation may explain cognitive impairment and cognitive fatigue in the chronic recovery phase of mild traumatic brain injury.

Generalized myositis mimicking polymyositis associated with chronic active Epstein-Barr virus infection.

PubMed

Uchiyama, Tomoyuki; Arai, Kimito; Yamamoto-Tabata, Takako; Hirai, Kanji; Kishimoto, Kouji; Nakamura, Yoshiko; Hattori, Takamichi

2005-05-01

Chronic generalized myositis has not so far been reported as a complication of chronic active Epstein-Barr virus infection (CAEBV). We encountered three patients with chronic generalized myositis mimicking polymyositis associated with CAEBV. To clarify the pathological character of this myositis, we investigated the distribution, clonality, and the immunophenotype of EBV-infected cells and lymphocytes infiltrating in muscles. Clinically, two patients showed symmetrical proximal weakness and muscle atrophy as the initial and main symptom. Although the condition resembled polymyositis, they had also lingual and/or orbital myositis. The other patient showed generalized myositis at the late phase of CAEBV. In all of them, immunotherapy was ineffective and prognosis was poor. Intramuscular infiltrating lymphocytes in our patients were mainly CD45RO+, CD3+, CD4-, CD8-, TCR betaF1-, TCR deltaTCS1-, CD56-, CD79a-, CD21-, HLA-DR+, ZEBRA -, LMP1-, and EBER+ T cells. Oligoclonal expansion of EBV-infected T cells was shown in the muscles. However, there were no malignant lymphocytes. This new form of myositis must be distinguished from polymyositis and the other conventional forms of myositis. Careful investigation of hidden CAEBV is recommended when patients present with steroid non-responsive chronic progressive generalized myositis, in particular, with lingual or orbital involvement.

Chronic myeloid leukemia with variation of translocation at (Ph) [ins (22;9) (q11;q21q34)]: a case report.

PubMed

Wang, Zhiqiong; Zen, Wen; Meng, Fankai; Xin, Xing; Luo, Li; Sun, Hanying; Zhou, Jianfeng; Huang, Lifang

2015-01-01

Chronic myeloid leukemia (CML) is most frequently observed in middle-aged individuals. In most patients, normal marrow cells are replaced by cells with an abnormal G-group chromosome, the Philadelphia (Ph) chromosome. The Ph chromosome that is characterized by the translocation (9;22) (q34;q11) is noted in 90-95% of patients diagnosed with CML. Studies have also shown that CML can be associated with various other cytogenetic abnormalities, with 5-10% of these cases showing complex translocation involving another chromosome in addition to the Ph chromosome. Here, we report the case of a Ph(+) CML patient with an inserted karyotype who presented clinically in the chronic phase but with atypical features. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

Measuring financial protection for health in families with chronic conditions in Rural China.

PubMed

Jiang, Chunhong; Ma, Jingdong; Zhang, Xiang; Luo, Wujin

2012-11-16

As the world's largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures. We used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient. An additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks. There is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods.

Measuring financial protection for health in families with chronic conditions in Rural China

PubMed Central

2012-01-01

Background As the world’s largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures. Methods We used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient. Results An additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks. Conclusions There is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods. PMID:23158260

Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke.

PubMed

Lomarev, M P; Kim, D Y; Richardson, S Pirio; Voller, B; Hallett, M

2007-09-01

Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic tool to rehabilitate chronic stroke patients. In this study, the safety of high-frequency rTMS in stroke was investigated (Phase I). The safety of 20 and 25 Hz rTMS over the motor cortex (MC) of the affected hemisphere, with intensities of 110-130% of the motor threshold (MT), was evaluated using surface electromyography (EMG) of hand and arm muscles. Brief EMG bursts, possibly representing peripheral manifestations of after discharges, and spread of excitation to proximal muscles are considered to be associated with a high risk of seizure occurrence. These events were recorded after the rTMS trains. Neither increased MC excitability nor improved pinch force dynamometry was found after rTMS. Stimulation parameters for rTMS, which are safe for healthy volunteers, may lead to a higher risk for seizure occurrence in chronic stroke patients. rTMS at rates of 20 and 25 Hz using above threshold stimulation potentially increases the risk of seizures in patients with chronic stroke.

Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study.

PubMed

Kreuzer, Peter M; Landgrebe, Michael; Resch, Markus; Husser, Oliver; Schecklmann, Martin; Geisreiter, Florian; Poeppl, Timm B; Prasser, Sarah J; Hajak, Goeran; Rupprecht, Rainer; Langguth, Berthold

2014-01-01

Vagus nerve stimulation represents an established treatment strategy for epilepsy and affective disorders. Recently, positive effects were also shown in animals and humans with tinnitus. Here we report the results of an open pilot study exploring feasibility, safety and efficacy of tVNS in the treatment of chronic tinnitus. Fifty patients with chronic tinnitus underwent tVNS in an open single-armed pilot study which was conducted in two phases applying two different stimulating devices (Cerbomed CM02 and NEMOS). Clinical assessment was based on Tinnitus Questionnaire (TQ), Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), WHO Quality of Life, and various numeric rating scales. Primary outcome was defined as change in TQ (baseline vs. final visit in week 24). The study has been registered with clinicaltrials.gov (NCT01176734). Primary analysis indicated mean TQ reductions of 3.7 points (phase 1) and 2.8 points (phase 2) significant for the first study phase. Secondary analyses indicated a significant BDI reduction for phase 1 (uncorrected for multiple testing), but no further systematic or significant effects. Adverse events included twitching and pressure at electrode placement site. The occurrence of one hospitalization because of palpations and the development of a left bundle branch block were considered as unrelated to the intervention. Cognitive testing revealed no significant changes. Our data demonstrate the feasibility of tVNS over a period of 6 months. There was no clinically relevant improvement of tinnitus complaints. Our data suggest tVNS to be considered safe in patients without a history of cardiac disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Evidence for induction of cytochrome P-450I in patients with tropical chronic pancreatitis.

PubMed

Chaloner, C; Sandle, L N; Mohan, V; Snehalatha, C; Viswanathan, M; Braganza, J M

1990-06-01

Theophylline kinetics, as an in vivo probe for the potentially toxic cytochrome P-450I pathway of drug metabolism, were studied in 11 healthy volunteers and 11 patients with calcific chronic pancreatitis at Madras, South India. Theophylline clearance was faster in the patients than controls [median 69 (range 39-114) vs 45 (33-56) ml h-1 kg-1, p = 0.003]. In keeping with this finding, detailed social histories identified a higher exposure level in the patients to xenobiotics that are inducers of cytochrome P-450I and/or yield reactive metabolites upon processing thereby (score 7, 4-11 vs 3, 2-9, p = 0.002). However, the concentration of D-glucaric acid in urine, as a marker of phase II conjugating pathways of drug metabolism, was similar in patients and controls. This pattern of drug metabolism could predispose to oxidant stress: hence micronutrient antioxidant supplements may have therapeutic (or even prophylactic) value in tropical chronic pancreatitis.

Antibody to hepatitis B core antigen levels in the natural history of chronic hepatitis B: a prospective observational study.

PubMed

Jia, Wei; Song, Liu-Wei; Fang, Yu-Qing; Wu, Xiao-Feng; Liu, Dan-Yang; Xu, Chun; Wang, Xiao-Mei; Wang, Wen; Lv, Dong-Xia; Li, Jun; Deng, Yong-Qiong; Wang, Yan; Huo, Na; Yu, Min; Xi, Hong-Li; Liu, Dan; Zhou, Yi-Xing; Wang, Gui-Qiang; Xia, Ning-Shao; Zhang, Ming-Xiang

2014-12-01

Previous studies have revealed antibody to hepatitis B core antigen (anti-HBc) levels as a predictor of treatment response in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in both interferon and nucleos(t)ide analog therapy cohorts. However, there is no information about anti-HBc levels in the natural history of CHB. This study aimed to define anti-HBc levels of different phases in the natural history of CHB. Two hundred eleven treatment-naive CHB patients were included in the study. They were classified into 4 phases: immune tolerance (IT) phase (n = 39), immune clearance (IC) phase (n = 48), low or no-replicative (LR) phase (n = 55), and HBeAg-negative hepatitis (ENH, n = 69). Fifty patients who were HBsAg negative and anti-HBc positive were also recruited as past HBV infection (PBI) control group. Anti-HBc levels were measured by a newly developed double-sandwich immunoassay. Correlation of anti-HBc levels with alanine aminotransferase (ALT) and other HBV-related markers within each phase was performed. Serum anti-HBc levels were statistically significant between patients in different phases of CHB (P < 0.001). The median anti-HBc levels were: IT (3.17 log 10 IU/mL), IC (4.39 log 10 IU/mL), LR (3.29 log 10 IU/mL), ENH (4.12 log 10 IU/mL), and PBI (0.61 log 10 IU/mL). There existed a strong correlation in IC (r = 0.489, P < 0.001), a poor correlation in ENH (r = 0.275, P = 0.042), and no correlation in patients with ALT reached 5 times upper limit of normal (r = 0.120, P = 0.616). Anti-HBc levels show significant differences during the natural course of CHB. These results may provide some potentially useful insights into hepatitis B pathogenesis and immune activation against hepatitis B virus.

Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199)

PubMed Central

Patel, Viralkumar M.; Balakrishnan, Kumudha; Douglas, Mark; Tibbitts, Thomas; Xu, Ethan Y.; Kutok, Jeffery L.; Ayers, Mary; Sarkar, Aloke; Guerrieri, Renato; Wierda, William G.; O’Brien, Susan; Jain, Nitin; Stern, Howard M.; Gandhi, Varsha

2017-01-01

Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin’s lymphoma (iNHL). In CLL, duvelisib monotherapy is associated with high iwCLL and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene-expression studies (RNA seq, Nanostring, Affymetrix array, and real time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes. In concert with induction of transcript levels, reverse phase protein arrays and immunoblots confirmed increase at the protein level. The BCL2 inhibitor venetoclax induced greater apoptosis in ex-vivo cultured CLL cells obtained from patients on duvelisib compared to pre-treatment CLL cells from the same patients. In vitro combination of duvelisib and venetoclax resulted in enhanced apoptosis even in CLL cells cultured under conditions that simulate the tumor microenvironment. These data provide a mechanistic rationale for testing the combination of duvelisib and venetoclax in the clinic. Such combination regimen (NCT02640833) is being evaluated for patients with B-cell malignancies including CLL. PMID:28017967

Enhancing mHealth Technology in the Patient-Centered Medical Home Environment to Activate Patients With Type 2 Diabetes: A Multisite Feasibility Study Protocol.

PubMed

Gimbel, Ronald; Shi, Lu; Williams, Joel E; Dye, Cheryl J; Chen, Liwei; Crawford, Paul; Shry, Eric A; Griffin, Sarah F; Jones, Karyn O; Sherrill, Windsor W; Truong, Khoa; Little, Jeanette R; Edwards, Karen W; Hing, Marie; Moss, Jennie B

2017-03-06

The potential of mHealth technologies in the care of patients with diabetes and other chronic conditions has captured the attention of clinicians and researchers. Efforts to date have incorporated a variety of tools and techniques, including Web-based portals, short message service (SMS) text messaging, remote collection of biometric data, electronic coaching, electronic-based health education, secure email communication between visits, and electronic collection of lifestyle and quality-of-life surveys. Each of these tools, used alone or in combination, have demonstrated varying degrees of effectiveness. Some of the more promising results have been demonstrated using regular collection of biometric devices, SMS text messaging, secure email communication with clinical teams, and regular reporting of quality-of-life variables. In this study, we seek to incorporate several of the most promising mHealth capabilities in a patient-centered medical home (PCMH) workflow. We aim to address underlying technology needs and gaps related to the use of mHealth technology and the activation of patients living with type 2 diabetes. Stated differently, we enable supporting technologies while seeking to influence patient activation and self-care activities. This is a multisite phased study, conducted within the US Military Health System, that includes a user-centered design phase and a PCMH-based feasibility trial. In phase 1, we will assess both patient and provider preferences regarding the enhancement of the enabling technology capabilities for type 2 diabetes chronic care management. Phase 2 research will be a single-blinded 12-month feasibility study that incorporates randomization principles. Phase 2 research will seek to improve patient activation and self-care activities through the use of the Mobile Health Care Environment with tailored behavioral messaging. The primary outcome measure is the Patient Activation Measure scores. Secondary outcome measures are Summary of Diabetes Self-care Activities Measure scores, clinical measures, comorbid conditions, health services resource consumption, and technology system usage statistics. We have completed phase 1 data collection. Formal analysis of phase 1 data has not been completed. We have obtained institutional review board approval and began phase 1 research in late fall 2016. The study hypotheses suggest that patients can, and will, improve their activation in chronic care management. Improved activation should translate into improved diabetes self-care. Expected benefits of this research to the scientific community and health care services include improved understanding of how to leverage mHealth technology to activate patients living with type 2 diabetes in self-management behaviors. The research will shed light on implementation strategies in integrating mHealth into the clinical workflow of the PCMH setting. ClinicalTrials.gov NCT02949037. https://clinicaltrials.gov/ct2/show/NCT02949037. (Archived by WebCite at http://www.webcitation.org/6oRyDzqei). ©Ronald Gimbel, Lu Shi, Joel E Williams, Cheryl J Dye, Liwei Chen, Paul Crawford, Eric A Shry, Sarah F Griffin, Karyn O Jones, Windsor W Sherrill, Khoa Truong, Jeanette R Little, Karen W Edwards, Marie Hing, Jennie B Moss. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 06.03.2017.

Phase angle as a nutritional evaluation tool in all stages of chronic liver disease.

PubMed

Peres, W A F; Lento, D F; Baluz, K; Ramalho, A

2012-01-01

Malnutrition is commonly and frequently under-diagnosed in clinical settings in patients with chronic liver disease (CLD) due to the limitations of nutritional evaluation methods in this population. We hypothesized that the bioelectrical impedance analysis derived phase angle (BIA-derived PhA) might be considered as a nutritional indicator in CLD since it represents either cell death or malnutrition characterized by changes in cellular membrane integrity. The aim of this study was to evaluate the BIA-derived PhA as a nutritional evaluation tool in all stages of CLD, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Liver-related death and survival were evaluated. A total of 66 patients were enrolled in a cross-sectional study. For the nutritional diagnosis, mid-arm circumference (MAC), triceps skinfold thickness (TST), mid-arm muscle circumference (MAMC) and Subject Global Assessment (SGA) were evaluated. Biochemical and clinical evaluations were performed. Our results showed that PhA was higher in well-nourished patients, according to SGA and in the patients without hepatic encephalopathy. PhA correlated significantly with MAMC, MAC and albumin and was inversely correlated with age. No correlation was found between PhA values and the Child-Pugh score and ascites. PhA was strongly associated with survival and PhA ≤ 5.18º with relative risk increase of 2.5 for death. We conclude that the BIA-derived PhA is a relevant nutritional evaluation tool in chronic hepatitis, liver cirrhosis and HCC and the role of PhA in the prediction of survival in CLD should be examined further in a controlled study.

Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal.

PubMed

Cortes, Jorge E; Talpaz, Moshe; O'Brien, Susan; Faderl, Stefan; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Verstovsek, Srdan; Rios, Mary B; Shan, Jenny; Kantarjian, Hagop M

2006-03-15

Several staging classification systems, all of which were designed in the preimatinib era, are used for chronic myeloid leukemia (CML). The World Health Organization (WHO) recently proposed a new classification system that has not been validated clinically. The authors investigated the significance of the WHO classification system and compared it with the classification systems used to date in imatinib trials ("standard definition") to determine its impact in establishing the outcome of patients after therapy with imatinib. In total, 809 patients who received imatinib for CML were classified into chronic phase (CP), accelerated phase (AP), and blast phase (BP) based on standard definitions and then were reclassified according to the new WHO classification system. Their outcomes with imatinib therapy were compared, and the value of individual components of these classification systems was determined. With the WHO classification, 78 patients (10%) were reclassified: 45 patients (6%) were reclassified from CP to AP, 14 patients (2%) were reclassified from AP to CP, and 19 patients (2%) were reclassified from AP to BP. The rates of complete cytogenetic response for patients in CP, AP, and BP according to the standard definition were 72%, 45%, and 8%, respectively. After these patients were reclassified according to WHO criteria, the response rates were 77% (P = 0.07), 39% (P = 0.28), and 11% (P = 0.61), respectively. The 3-year survival rates were 91%, 65%, and 10%, respectively, according to the standard classification and 95% (P = 0.05), 63% (P = 0.76), and 16% (P = 0.18), respectively, according to the WHO classification. Patients who had a blast percentage of 20-29%, which is considered CML-BP according to the WHO classification, had a significantly better response rate (21% vs. 8%; P = 0.11) and 3-year survival rate (42% vs. 10%; P = 0.0001) compared with patients who had blasts > or = 30%. Different classification systems had an impact on the outcome of patients, and some prognostic features had different prognostic implications in the imatinib era. The authors believe that a new, uniform staging system for CML is warranted, and they propose such a system. (c) 2006 American Cancer Society.

Natural history of chronic hepatitis B virus infection from infancy to adult life - the mechanism of inflammation triggering and long-term impacts.

PubMed

Wu, Jia-Feng; Chang, Mei-Hwei

2015-10-20

Chronic hepatitis B virus (HBV) infection in endemic areas usually starts since infancy and early childhood and persists lifelong. The clinical course varies among different chronic infected subjects. Majority of chronic HBV infected children present with immune-tolerant status initially, experience the immune clearance phase with various degree of liver injury during or beyond puberty, and then enter the inactive phase after hepatitis B e antigen (HBeAg) seroconversion. Part of them may have HBV DNA titers elevation with hepatitis flare after HBeAg seroconversion, the so call HBeAg-negative hepatitis flare. Liver cirrhosis, and even hepatocellular carcinoma may develop afterward.The complex course of chronic HBV infection is associated with the age/route of viral acquisition, host factors such as immune and endocrine factors, viral factors, and host-viral interactions. The adrenarche and puberty onset modulate the start of immune clearance and the severity of liver inflammation in chronic HBV infected children. The genotype and phenotype of human cytokines, innate immunity, and human leukocyte antigens are also associated with the onset of immune clearance of HBV and severity of inflammation. Immune escape HBV mutant strains, emerged during the immune clearance phase under host immune surveillance, may cause different impacts on viral biosynthesis, host immune responses, and clinical course.Early events in childhood during chronic HBV infection may serve as important predictors for the later outcome in adulthood. Understanding the mechanisms triggering liver inflammation and their long-term impacts may enhance the development of better and earlier therapeutic strategies for patients with chronic HBV infection.

The natural history of acute hepatitis C: clinical presentation, laboratory findings, and treatment outcomes

PubMed Central

Loomba, R.; Rivera, M. M.; McBurney, R.; Park, Y.; Haynes-Williams, V.; Rehermann, B.; Alter, H. J.; Herrine, S. K.; Liang, T. J.; Hoofnagle, J. H.; Heller, T.

2017-01-01

Summary Background Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. Aims To establish natural history and complications of treatment of acute hepatitis C. Methods Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Results Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and HCV RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4 to 8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Conclusion Thus, among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Antiviral treatment with a 24-week course of peginterferon and ribavirin was highly effective but marked by frequent and severe side effects. PMID:21198704

Early and late management of type B aortic dissection.

PubMed

Nienaber, Christoph A; Divchev, Dimitar; Palisch, Holger; Clough, Rachel E; Richartz, Barbara

2014-10-01

The management of type B aortic dissection is undergoing profound changes with timely TEVAR accepted as first-line strategy in the setting of complicated dissection; with recent technological advances and in experienced hands this intervention is considered safe and life-saving. With the ability to remodel the dissected aorta as a result of scaffolding even pre-emptive endovascular treatment is being considered and supported by long-term stability and often prevention of aneurysmal expansion. This insight and a growing number of silent risk conditions (resistant hypertension, partial false lumen thrombosis) may lower the threshold for TEVAR in asymptomatic patients in the subacute phase. In the chronic phase of a type B dissection patients are usually free of symptoms, however, with the expanding false lumen at risk of rupture. Advanced TEVAR options (including branches and fenestrations) are likely to be used more often than open surgical replacement of such aneurysmatic segment of the dissected aorta in that chronic phase. All dissection patients should be offered lifelong surveillance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B.

PubMed

Chen, En-Qiang; Feng, Shu; Wang, Meng-Lan; Liang, Ling-Bo; Zhou, Ling-Yun; Du, Ling-Yao; Yan, Li-Bo; Tao, Chuan-Min; Tang, Hong

2017-03-14

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

Efficient collection of peripheral blood stem cells using the Fresenius AS104 in chronic myelocytic leukemia patients with very high numbers of platelets.

PubMed

Komatsu, F; Ishida, Y

1997-04-01

For chronic myelocytic leukemia patients with very high numbers of platelets, we describe an efficient method for the collection of peripheral blood stem cells (PBSC) using the Fresenius AS104 cell separator. In these patients, it is difficult to collect a sufficient number of PBSC, due to the platelet band interfering with the machine's red cell interface sensor. We, therefore, tried a manual adjustment of the device. The collection phase was set automatically. When the whole blood began to separate into the red cell layer and plasma (plus mononuclear cell) layer, the red cell interface setting of "7:1" was changed to "OFF," and the plasma pump flow rate was controlled manually in order to locate the interface position 1 cm from the outside wall of the centrifuge chamber. After the collection phase, the procedure was returned to the automatic setting. By repeating this procedure, we were able to collect large numbers of PBSC.

Adequate Initial Antidepressant Treatment Among Patients With Chronic Obstructive Pulmonary Disease in a Cohort of Depressed Veterans

PubMed Central

Pirraglia, Paul A.; Charbonneau, Andrea; Kader, Boris; Berlowitz, Dan R.

2006-01-01

Objective: Depression is common among patients with chronic obstructive pulmonary disease (COPD). Patients with COPD may be more likely to have inadequate treatment with antidepressant medications. We tested the hypothesis that depressed patients with COPD have lower odds of adequate duration of antidepressant therapy in the first 3 months of treatment compared to those without COPD. Method: Using administrative and centralized pharmacy data from 14 northeastern Veterans Affairs Medical Centers, we identified 778 veterans with depression (ICD-9-CM codes 296.2x, 296.3x, and 311.xx) who were in the acute phase of antidepressant treatment from June 1, 1999, through August 31, 1999. Within this group, we identified those patients with COPD (23%). An adequate duration of antidepressant treatment was defined as ≥ 80% of days on an antidepressant. We used multivariable logistic regression models to determine the adjusted odds of adequate acute phase antidepressant treatment duration. Results: Those patients with COPD had markedly lower odds of adequate acute phase treatment duration (odds ratio = 0.67, 95% CI = 0.47 to 0.96); this was not observed with other medical diagnoses such as coronary heart disease, diabetes mellitus, or osteoarthritis. Conclusions: The first few months of treatment appears to be a critical period for depressed patients with COPD who are started on antidepressants. The causes for early antidepressant treatment inadequacy among patients with COPD require further investigation. More intensive efforts may be necessary early in the course of treatment to assure high-quality pharmacologic therapy of depressed patients with COPD. PMID:16862230

Evaluating a novel health system intervention for chronic kidney disease care using the RE-AIM framework: Insights after two years.

PubMed

Hynes, Denise M; Fischer, Michael J; Schiffer, Linda A; Gallardo, Rani; Chukwudozie, Ifeanyi Beverly; Porter, Anna; Berbaum, Michael; Earheart, Jennifer; Fitzgibbon, Marian L

2017-01-01

Using a quasi-experimental design, we implemented the Patient-Centered Medical Home for Kidney Disease (PCMH-KD), a comprehensive, multidisciplinary care team to improve quality of life and healthcare coordination for adult chronic hemodialysis (CHD) patients. This paper highlights our experience in the first two years of the study. We focus on the process dimensions of Reach, Adoption, and Implementation within the context of the RE-AIM framework. We established a new PCMH-KD model at two outpatient dialysis centers. During the intervention phase, adult patients were recruited for participation and data collection. We monitored RE-AIM measures to identify areas for potential adaptation of the care model. During the start-up phase, we engaged patients and stakeholders in planning the intervention, established the new PCMH-KD team, and trained new and continuing clinicians and staff at two dialysis centers. In the intervention phase we recruited 155 patients to participate. Patients had individual visits with the PCP (40%) and the CHWs (92%) (Reach). Patient feedback informed procedures for appointment scheduling (Adoption). The new PCMH-KD team members were consistent in their roles. With staff changes, some responsibilities were adapted for cross coverage (Implementation). After one year of start-up and one year of intervention, active monitoring of Reach, Implementation and Adoption measures have facilitated necessary adaptions in the planned intervention to accommodate scheduling demands and patient feedback in the PCMH-KD model. Insights from this trial may inform care of CHD patients more broadly. Copyright © 2016. Published by Elsevier Inc.

Tildrakizumab: First Global Approval.

PubMed

Markham, Anthony

2018-05-11

Merck & Company Inc. have developed tildrakizumab (tildrakizumab-asmn; Ilumya™), a high-affinity, humanised IgG1 κ monoclonal antibody that specifically targets interleukin-23 p19, as a treatment for chronic plaque psoriasis. The drug was recently approved for marketing by the US FDA based on positive results from the phase III reSURFACE clinical trial programme in patients with chronic plaque psoriasis. This article summarizes the milestones in the development of tildrakizumab leading to this first approval for the treatment of adults with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

Guide for Instructors of Practical Nursing in South Carolina, Phase 2.

ERIC Educational Resources Information Center

Clemson Univ., SC. Vocational Education Media Center.

The South Carolina Department of Education has printed an instruction manual for teacher use in schools of nursing. The guide covers the areas of medical surgical nursing, diagnosis of disease, dealing with the surgical patient, care of the aged, rehabilitation and chronic illness, nursing the cancer patient, gynecological disorders, respiratory…

Upper-Limb Exercises for Stroke Patients through the Direct Engagement of an Embodied Agent

DTIC Science & Technology

2011-03-01

hemiparesis . To alleviate impairments, pa- tients pursue therapy services at the acute, sub-acute, and chronic phases as necessary. Patients need...year-old male who suffered from a stroke 15 years ago. He has right hemiparesis and ambu- lates with a quad cane. He has limited scapula and minimal

Characterization of Patients with Chronic Myeloid Leukemia Unresponsive to Tyrosine Kinase Inhibitors Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Carvalho, Franceli Ramos; Zuckermann, Joice; Paz, Alessandra; Fischer, Gustavo; Daudt, Liane Esteves; Rigoni, Lisandra Della Costa; Silla, Lúcia; Fogliatto, Laura; de Castro, Simone Martins; Pilger, Diogo André

2017-01-01

Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure. Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014. Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT. Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.

Characterization of Patients with Chronic Myeloid Leukemia Unresponsive to Tyrosine Kinase Inhibitors Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Carvalho, Franceli Ramos; Zuckermann, Joice; Paz, Alessandra; Fischer, Gustavo; Daudt, Liane Esteves; Rigoni, Lisandra Della Costa; Silla, Lúcia; Fogliatto, Laura; de Castro, Simone Martins; Pilger, Diogo André

2017-01-01

Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure. Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014. Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT. Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT. PMID:28286612

Higher Dose Imatinib for Children With De Novo Chronic Phase Chronic Myelogenous Leukemia: A Report From the Children’s Oncology Group

PubMed Central

Champagne, Martin A.; Fu, Cecilia H.; Chang, Myron; Chen, Helen; Gerbing, Robert B.; Alonzo, Todd A.; Cooley, Linda D.; Heerema, Nyla A.; Oehler, Vivian; Wood, Charlotte; French, Mary Ellen; Arceci, Robert J.; Smith, Franklin O.; Bernstein, Mark L.

2016-01-01

Purpose To determine the efficacy of imatinib in children with newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML). Methods This was an open label, multi-center phase II clinical trial. Courses were defined as consecutive 28-day intervals. Oral imatinib was administered daily at 340 mg/m2 without interruption in the absence of toxicity. Results Fifty-one children received 978 28-day courses of imatinib. The most common toxicities encountered were hematologic. Forty-one patients (80%) achieved a complete hematologic response by the end of course 2. Nineteen children (38%) obtained a complete cytogenetic response (CCyR) at the end of course 3. Overall, 72% achieved CCyR at a median time of 5.6 months. The rate of complete molecular response (>3 log reduction) was 27%. Progression-free and overall survival at 3 years were 72% ± 6.4% and 92% ± 3.9%, respectively. Conclusions Daily oral imatinib at a dose of 340 mg/m2 is well tolerated in children. In addition, imatinib therapy is effective in inducing a high percent of hematologic, cytogenetic and molecular responses, comparable to adults with CML. PMID:21465636

At-Home Transcranial Direct Current Stimulation (tDCS) With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms.

PubMed

Riggs, Alexa; Patel, Vaishali; Paneri, Bhaskar; Portenoy, Russell K; Bikson, Marom; Knotkova, Helena

2018-01-01

Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications. Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support. Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS) and a tDCS user survey. Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10-20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients' training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and there were no adverse events. Data collection was feasible and there were no missing data. Satisfaction with the tDCS-telehealth procedure was high and the patients were comfortable using the system. Conclusion: At-home tDCS with telehealth support appears to be a feasible approach for the management of symptom burden in patients with chronic illness. Further studies to evaluate and optimize the protocol effectiveness for symptom-control outcomes are warranted.

Cost of illness of oral lichen planus in a U.K. population--a pilot study.

PubMed

Ni Riordain, Richeal; Christou, Joanna; Pinder, Denise; Squires, Vanessa; Hodgson, Tim

2016-05-01

To assess the economic burden of oral lichen planus (OLP) from the perspective of the healthcare provider in a U.K. population. This prevalence-based cost-of-illness analysis was carried out via a cross-sectional study conducted in the Oral Medicine Unit of the Eastman Dental Hospital. This study was conducted in three phases - phase 1 involved framing of the cost-of-illness analysis, development of the cost inventory and design of the patient questionnaire for ease of data collection. Data collected from patients were inputted during phase 2, and costings were determined. The final phase consisted of the calculation of the cost of illness of OLP. One hundred patients were enrolled in the study, 30 males and 70 females, with an average age of 59.9 years (±13.4 years). The average OLP patient, based on our cohort, attends the oral medicine unit 2.64 times per year, their general medical practitioner 1.13 times annually, their general dental practitioner 0.82 times in a year and fills on average 3.37 prescriptions annually. This leads to an average annual cost of £398.58 (€541.16) per patient per year from the perspective of the healthcare provider. The annual average cost of OLP to the healthcare provider in the U.K. is substantial. The prevalence-based cost-of-illness data generated in this study will facilitate comparison with other chronic oral mucosal diseases and with chronic diseases managed in allied medical specialties. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Safety and tolerability review of lorcaserin in clinical trials.

PubMed

Greenway, F L; Shanahan, W; Fain, R; Ma, T; Rubino, D

2016-10-01

Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations. © 2016 World Obesity.

A Web-Based Decision Tool to Improve Contraceptive Counseling for Women With Chronic Medical Conditions: Protocol For a Mixed Methods Implementation Study

PubMed Central

Damschroder, Laura J; Fetters, Michael D; Zikmund-Fisher, Brian J; Crabtree, Benjamin F; Hudson, Shawna V; Ruffin IV, Mack T; Fucinari, Juliana; Kang, Minji; Taichman, L Susan; Creswell, John W

2018-01-01

Background Women with chronic medical conditions, such as diabetes and hypertension, have a higher risk of pregnancy-related complications compared with women without medical conditions and should be offered contraception if desired. Although evidence based guidelines for contraceptive selection in the presence of medical conditions are available via the United States Medical Eligibility Criteria (US MEC), these guidelines are underutilized. Research also supports the use of decision tools to promote shared decision making between patients and providers during contraceptive counseling. Objective The overall goal of the MiHealth, MiChoice project is to design and implement a theory-driven, Web-based tool that incorporates the US MEC (provider-level intervention) within the vehicle of a contraceptive decision tool for women with chronic medical conditions (patient-level intervention) in community-based primary care settings (practice-level intervention). This will be a 3-phase study that includes a predesign phase, a design phase, and a testing phase in a randomized controlled trial. This study protocol describes phase 1 and aim 1, which is to determine patient-, provider-, and practice-level factors that are relevant to the design and implementation of the contraceptive decision tool. Methods This is a mixed methods implementation study. To customize the delivery of the US MEC in the decision tool, we selected high-priority constructs from the Consolidated Framework for Implementation Research and the Theoretical Domains Framework to drive data collection and analysis at the practice and provider level, respectively. A conceptual model that incorporates constructs from the transtheoretical model and the health beliefs model undergirds patient-level data collection and analysis and will inform customization of the decision tool for this population. We will recruit 6 community-based primary care practices and conduct quantitative surveys and semistructured qualitative interviews with women who have chronic medical conditions, their primary care providers (PCPs), and clinic staff, as well as field observations of practice activities. Quantitative survey data will be summarized with simple descriptive statistics and relationships between participant characteristics and contraceptive recommendations (for PCPs), and current contraceptive use (for patients) will be examined using Fisher exact test. We will conduct thematic analysis of qualitative data from interviews and field observations. The integration of data will occur by comparing, contrasting, and synthesizing qualitative and quantitative findings to inform the future development and implementation of the intervention. Results We are currently enrolling practices and anticipate study completion in 15 months. Conclusions This protocol describes the first phase of a multiphase mixed methods study to develop and implement a Web-based decision tool that is customized to meet the needs of women with chronic medical conditions in primary care settings. Study findings will promote contraceptive counseling via shared decision making and reflect evidence-based guidelines for contraceptive selection. Trial Registration ClinicalTrials.gov NCT03153644; https://clinicaltrials.gov/ct2/show/NCT03153644 (Archived by WebCite at http://www.webcitation.org/6yUkA5lK8) PMID:29669707

Communication about chronic critical illness.

PubMed

Nelson, Judith E; Mercado, Alice F; Camhi, Sharon L; Tandon, Nidhi; Wallenstein, Sylvan; August, Gary I; Morrison, R Sean

2007-12-10

Despite poor outcomes, life-sustaining treatments including mechanical ventilation are continued for a large and growing population of patients with chronic critical illness. This may be owing in part to a lack of understanding resulting from inadequate communication between clinicians and patients and families. Our objective was to investigate the informational needs of patients with chronic critical illness and their families and the extent to which these needs are met. In this prospective observational study conducted at 5 adult intensive care units in a large, university-affiliated hospital in New York, New York, 100 patients with chronic critical illness (within 3-7 days of elective tracheotomy for prolonged mechanical ventilation) or surrogates for incapacitated patients were surveyed using an 18-item questionnaire addressing communication about chronic critical illness. Main outcome measures included ratings of importance and reports of whether information was received about questionnaire items. Among 125 consecutive, eligible patients, 100 (80%) were enrolled; questionnaire respondents included 2 patients and 98 surrogates. For all items, more than 78% of respondents rated the information as important for decision making (>98% for 16 of 18 items). Respondents reported receiving no information for a mean (SD) of 9.0 (3.3) of 18 items, with 95% of respondents reporting not receiving information for approximately one-quarter of the items. Of the subjects rating the item as important, 77 of 96 (80%) and 69 of 74 (93%) reported receiving no information about expected functional status at hospital discharge and prognosis for 1-year survival, respectively. Many patients and their families may lack important information for decision making about continuation of treatment in the chronic phase of critical illness. Strategies for effective communication in this clinical context should be investigated and implemented.

Communication About Chronic Critical Illness

PubMed Central

Nelson, Judith E.; Mercado, Alice F.; Camhi, Sharon L.; Tandon, Nidhi; Wallenstein, Sylvan; August, Gary I.; Morrison, R. Sean

2008-01-01

Background Despite poor outcomes, life-sustaining treatments including mechanical ventilation are continued for a large and growing population of patients with chronic critical illness. This may be owing in part to a lack of understanding resulting from inadequate communication between clinicians and patients and families. Our objective was to investigate the informational needs of patients with chronic critical illness and their families and the extent to which these needs are met. Methods In this prospective observational study conducted at 5 adult intensive care units in a large, university-affiliated hospital in New York, New York, 100 patients with chronic critical illness (within 3–7 days of elective tracheotomy for prolonged mechanical ventilation) or surrogates for incapacitated patients were surveyed using an 18-item questionnaire addressing communication about chronic critical illness. Main outcome measures included ratings of importance and reports of whether information was received about questionnaire items. Results Among 125 consecutive, eligible patients, 100 (80%) were enrolled; questionnaire respondents included 2 patients and 98 surrogates. For all items, more than 78% of respondents rated the information as important for decision making (>98% for 16 of 18 items). Respondents reported receiving no information for a mean (SD) of 9.0 (3.3) of 18 items, with 95% of respondents reporting not receiving information for approximately one-quarter of the items. Of the subjects rating the item as important, 77 of 96 (80%) and 69 of 74 (93%) reported receiving no information about expected functional status at hospital discharge and prognosis for 1-year survival, respectively. Conclusions Many patients and their families may lack important information for decision making about continuation of treatment in the chronic phase of critical illness. Strategies for effective communication in this clinical context should be investigated and implemented. PMID:18071175

Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial.

PubMed

Jones, Jeffrey A; Mato, Anthony R; Wierda, William G; Davids, Matthew S; Choi, Michael; Cheson, Bruce D; Furman, Richard R; Lamanna, Nicole; Barr, Paul M; Zhou, Lang; Chyla, Brenda; Salem, Ahmed Hamed; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Coutre, Steven; Woyach, Jennifer; Byrd, John C

2018-01-01

Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy. In this interim analysis of a multicentre, open-label, non-randomised, phase 2 trial, we enrolled patients aged 18 years or older with a documented diagnosis of chronic lymphocytic leukaemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance score of 2 or lower. All patients had relapsed or refractory disease after previous treatment with a BCR signalling pathway inhibitor. All patients were screened for Richter's transformation and cases confirmed by biopsy were excluded. Eligible patients received oral venetoclax, starting at 20 mg per day with stepwise dose ramp-up over 5 weeks to 400 mg per day. Patients with rapidly progressing disease received an accelerated dosing schedule (to 400 mg per day by week 3). The primary endpoint was overall response, defined as the proportion of patients with an overall response per investigator's assessment according to IWCLL criteria. All patients who received at least one dose of venetoclax were included in the activity and safety analyses. This study is ongoing; data for this interim analysis were collected per regulatory agencies' request as of June 30, 2017. This trial is registered with ClinicalTrials.gov, number NCT02141282. Between September, 2014, and November, 2016, 127 previously treated patients with relapsed or refractory chronic lymphocytic leukaemia were enrolled from 15 sites across the USA. 91 patients had received ibrutinib as the last BCR inhibitor therapy before enrolment, 43 of whom were enrolled in the main cohort and 48 in the expansion cohort recruited later after a protocol amendment. At the time of analysis, the median follow-up was 14 months (IQR 8-18) for all 91 patients, 19 months (9-27) for the main cohort, and 12 months (8-15) for the expansion cohort. 59 (65%, 95% CI 53-74) of 91 patients had an overall response, including 30 (70%, 54-83) of 43 patients in the main cohort and 29 (60%, 43-72) of 48 patients in the expansion cohort. The most common treatment-emergent grade 3 or 4 adverse events were neutropenia (46 [51%] of 91 patients), thrombocytopenia (26 [29%]), anaemia (26 [29%]), decreased white blood cell count (17 [19%]), and decreased lymphocyte count (14 [15%]). 17 (19%) of 91 patients died, including seven because of disease progression. No treatment-related deaths occurred. The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory chronic lymphocytic leukaemia whose disease progressed during or after discontinutation of ibrutinib therapy. The durability of response to venetoclax will be assessed in the final analysis in 2019. AbbVie, Genentech. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain.

PubMed

Moseley, G Lorimer; Zalucki, Nadia M; Wiech, Katja

2008-07-31

Chronic pain is often associated with reduced tactile acuity. A relationship exists between pain intensity, tactile acuity and cortical reorganisation. When pain resolves, tactile function improves and cortical organisation normalises. Tactile acuity can be improved in healthy controls when tactile stimulation is associated with a behavioural objective. We hypothesised that, in patients with chronic limb pain and decreased tactile acuity, discriminating between tactile stimuli would decrease pain and increase tactile acuity, but tactile stimulation alone would not. Thirteen patients with complex regional pain syndrome (CRPS) of one limb underwent a waiting period and then approximately 2 weeks of tactile stimulation under two conditions: stimulation alone or discrimination between stimuli according to their diameter and location. There was no change in pain (100 mm VAS) or two-point discrimination (TPD) during a no-treatment waiting period, nor during the stimulation phase (p > 0.32 for both). Pain and TPD were lower after the discrimination phase [mean (95% CI) effect size for pain VAS = 27 mm (14-40 mm) and for TPD = 5.7 mm (2.9-8. ), p < 0.015 for both]. These gains were maintained at three-month follow-up. We conclude that tactile stimulation can decrease pain and increase tactile acuity when patients are required to discriminate between the type and location of tactile stimuli.

Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.

PubMed

Nair, Anish P; Barnett, Michael J; Broady, Raewyn C; Hogge, Donna E; Song, Kevin W; Toze, Cynthia L; Nantel, Stephen H; Power, Maryse M; Sutherland, Heather J; Nevill, Thomas J; Abou Mourad, Yasser; Narayanan, Sujaatha; Gerrie, Alina S; Forrest, Donna L

2015-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P < .0001). Donor (female) to patient (male) gender combination (P = .02) and CMR to HSCT (P < .0001) predicted lower relapse. In multivariate analysis, CMR to HSCT remained an independent predictor of OS (odds ratio [OR], 43), EFS (OR, 56) and relapse (OR, 29). This report indicates that the outlook is excellent for those patients who remain in CP1 at the time of HSCT and achieve a CMR after HSCT. However, only approximately 50% of those in advanced phase at HSCT are long-term survivors. This highlights the ongoing need to try to identify patients earlier, before disease progression, who are destined to fail this treatment to optimize transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016.

PubMed

von Haehling, Stephan; Anker, Markus S; Anker, Stefan D

2016-12-01

Cachexia is a serious clinical consequence of almost all chronic diseases when reaching advanced stages. Its prevalence ranges from 5-15% in end-stage chronic heart failure to 50-80% in advanced malignant cancer. Cachexia is also frequently occurring in patients with chronic kidney disease, chronic obstructive pulmonary disease (COPD) or neurological diseases, and rheumatoid arthritis. Mortality rates of patients with cachexia range from 15-25% per year in severe COPD through 20-40% per year in patients with chronic heart failure or chronic kidney disease to 20-80% in cancer cachexia. In the industrialized world (North America, Europe, and Japan) where epidemiological data are to some degree available, the overall prevalence of cachexia (due to any disease and not necessarily associated with hospital admission) is growing with the growth of the chronic illness prevalence, and it currently affects around 0.5-1.0% of the population, i.e. around 6-12 million people. From this, one can estimate that 1.5-2 million deaths are occurring in patients with cachexia per year. It is also a very significant health problem in other parts of the globe, but epidemiological data are scarce. The multifactorial nature of cachexia is now much better understood, and particularly, the role of inflammatory mediators and the imbalance of anabolism and catabolism are considered important therapeutic targets. Several approaches to develop cachexia and muscle wasting treatments have failed to be successful in phase III clinical trials, but new approaches are in development. Given the high prevalence and very high mortality associated with cachexia, advances are urgently needed for patients worldwide.

Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016

PubMed Central

von Haehling, Stephan; Anker, Markus S.

2016-01-01

Abstract Cachexia is a serious clinical consequence of almost all chronic diseases when reaching advanced stages. Its prevalence ranges from 5–15% in end‐stage chronic heart failure to 50–80% in advanced malignant cancer. Cachexia is also frequently occurring in patients with chronic kidney disease, chronic obstructive pulmonary disease (COPD) or neurological diseases, and rheumatoid arthritis. Mortality rates of patients with cachexia range from 15–25% per year in severe COPD through 20–40% per year in patients with chronic heart failure or chronic kidney disease to 20–80% in cancer cachexia. In the industrialized world (North America, Europe, and Japan) where epidemiological data are to some degree available, the overall prevalence of cachexia (due to any disease and not necessarily associated with hospital admission) is growing with the growth of the chronic illness prevalence, and it currently affects around 0.5–1.0% of the population, i.e. around 6–12 million people. From this, one can estimate that 1.5–2 million deaths are occurring in patients with cachexia per year. It is also a very significant health problem in other parts of the globe, but epidemiological data are scarce. The multifactorial nature of cachexia is now much better understood, and particularly, the role of inflammatory mediators and the imbalance of anabolism and catabolism are considered important therapeutic targets. Several approaches to develop cachexia and muscle wasting treatments have failed to be successful in phase III clinical trials, but new approaches are in development. Given the high prevalence and very high mortality associated with cachexia, advances are urgently needed for patients worldwide. PMID:27891294

A successful renal transplantation for renal failure after dasatinib-induced thrombotic thrombocytopenic purpura in a patient with imatinib-resistant chronic myelogenous leukaemia on nilotinib.

PubMed

Martino, Suella; Daguindau, Etienne; Ferrand, Christophe; Bamoulid, Jamal; Hayette, Sandrine; Nicolini, F-E; Capellier, G; Deconinck, Eric; Larosa, Fabrice

2013-01-01

Second-generation tyrosine kinase inhibitors (TKI2) often induce molecular remission, and prolonged survival with a better tolerance in imatinib-resistant chronic myelogenous leukaemia (CML) patients. We report the case of a CML in first chronic phase who was diagnosed in August 2003 in a young 24 year-old Caucasian woman. Our patient received first imatinib and then dasatinib and nilotinib. Imatinib was well tolerated and she developed TTP/HUS on dasatinib without documented evolution of CML and finally obtained MR5.0 with nilotinib and without any side effect. This case also illustrates the absence of cross-resistance and side-effects between the different TKIs and the feasibility of kidney transplantation associated with a nilotinib treatment of CML allowing a continuing MR5.0 and no further side effects.

Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.

PubMed

Sharman, Jeff P; Farber, Charles M; Mahadevan, Daruka; Schreeder, Marshall T; Brooks, Heather D; Kolibaba, Kathryn S; Fanning, Suzanne; Klein, Leonard; Greenwald, Daniel R; Sportelli, Peter; Miskin, Hari P; Weiss, Michael S; Burke, John M

2017-02-01

Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156). © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

A pilot study on community-based outpatient treatment for patients with chronic psychotic disorders in Somalia: Change in symptoms, functioning and co-morbid khat use

PubMed Central

2012-01-01

Background In Low and Middle Income Countries, mental health services are often poorly developed due to the lack of resources and trained personnel. In order to overcome these challenges, new ways of care have been suggested such as a focus on community-based services. In Somalia, the consumption of the natural stimulant khat is highly prevalent, aggravating mental illness. At the same time, mental health care is largely unavailable to the vast majority of the population. In a pilot project, we tested possibilities for effective measures in community-based out-patient mental health care. Methods Thirty-five male patients with chronic psychotic disorders and their carers were involved in a 10-months follow-up study. All of them abused khat. Seventeen outpatients experiencing acute psychotic episodes were recruited from the community and received an intensive six week home-based treatment package. Additionally eighteen patients with chronic psychotic disorders in remission were recruited either following hospital discharge or from the community. In a second phase of the study, both groups received community-based relapse prevention that differed in the degree of the family’s responsibility for the treatment. The treatment package was comprised of psycho-education, low-dose neuroleptic treatment, monthly home visits and counseling. The Brief Psychiatric Rating Scale (BPRS) was applied three times. Additionally, we assessed functioning, khat use and other outcomes. Results Of the 35 patients enrolled in the study, 33 participated in the 10-month follow-up. Outpatients improved significantly in the first six weeks of treatment and did not differ from remitted patients at the start of the second treatment phase. In the preventive treatment phase, we find heterogeneous outcomes that diverge between symptom and functioning domains. With the exception of depressive symptoms, symptoms in all patients tended to worsen. The outpatient group had higher BPRS positive and negative symptom scores compared to the remitted group. Levels of functioning in 20 out of 33 patients significantly improved, with small differences between groups. Most patients experienced improvements in basic functioning, such as communication, self-care etc. Khat use could only be reduced in the group of outpatients. Conclusions Community-based out-patient mental health treatment for chronic psychotic disorders has demonstrated positive effects in Somalia and is both feasible and practical, despite facing formidable challenges, e.g. controlling khat intake. PMID:22747911

Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-04-05

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Inflammation and glandular duct dilatation of the tongue from patients with chronic Chagas disease.

PubMed

de Lima Pereira, Sanívia Aparecida; Rodrigues, Denise Bertulucci Rocha; da Fonseca Ferraz, Mara Lúcia; da Cunha Castro, Eumenia Costa; dos Reis, Marlene Antonia; de Paula Antunes Teixeira, Vicente

2006-01-01

The purpose of this study was to evaluate morphologically the tongue of individuals with chronic Chagas disease (CD) in comparison to the non-chagasic ones. Twenty-four protocol cases of autopsies were selected. They were subdivided into CD patients (10 cases) and non-chagasic ones (14 cases). The morphometric analysis was accomplished for the tongue muscle and salivary glands duct lumen area. In three CD patients, perineuritis was found, and two of them showed megaesophagus and megacolon. The intensity of the inflammation in the von Ebner's glands, the tongue muscles, and the salivary glands duct lumen area was significantly higher in the CD patients. We concluded that the CD patients show salivary glands duct dilatation, which probably would have a relation with alterations in the autonomic nervous system. The inflammation found in CD patients is in accordance with that described in comparative studies on the digestive tract and heart. These morphological findings suggest that the histopathological analysis of the tongue associated with other organs, or even in an isolated manner, can add in the diagnosis and pathogenesis of the CD chronic phase.

High cost sharing and specialty drug initiation under Medicare Part D: a case study in patients with newly diagnosed chronic myeloid leukemia.

PubMed

Doshi, Jalpa A; Li, Pengxiang; Huo, Hairong; Pettit, Amy R; Kumar, Rishab; Weiss, Brenda M; Huntington, Scott F

2016-03-01

Specialty drugs often offer medical advances but are frequently subject to high cost sharing. This is particularly true with Medicare Part D, where after meeting a deductible, patients without low-income subsidies (non-LIS) typically face 25% to 33% coinsurance (initial coverage phase with "specialty tier" cost sharing), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). Yet, no studies have examined the impact of such high cost sharing on specialty drug initiation under Part D. Oral tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it an apt case study. A retrospective claims-based analysis utilizing 2011 to 2013 100% Medicare claims. TKI initiation rates and time to initiation were compared between fee-for-service non-LIS Part D patients newly diagnosed with CML and their LIS counterparts who faced nominal cost sharing of ≤ $5. The first 30-day TKI fill "straddled" benefit phases, for a mean out-of-pocket cost of $2600 or more for non-LIS patients. Non-LIS patients were less likely than LIS patients to have a TKI claim within 6 months of diagnosis (45.3% vs 66.9%; P < .001) and those initiating a TKI took twice as long to fill it (mean = 50.9 vs 23.7 days; P < .001). Cox regressions controlling for sociodemographic, clinical, and plan characteristics confirmed descriptive findings (hazard ratio, 0.59; 95% CI, 0.45-0.76). Extensive sensitivity analyses confirmed the robustness of our findings. High cost sharing was associated with reduced and/or delayed initiation of TKIs. We discuss policy strategies to reduce current financial barriers that adversely impact access to critical therapies under Medicare Part D.

Blastic transformation in chronic myelogenous leukemia: experience with 50 patients.

PubMed

Marks, S M; McCaffrey, R; Rosenthal, D S; Moloney, W C

1978-01-01

Fifty consecutive patients with blastic chronic myelogenous leukemia were evaluated clinically, morphologically, biochemically, and therapeutically. Forty-five patients had a preceding stable phase (38 Ph'+, 7 Ph'-); five patients presented with de novo Ph+ blast crisis. The most frequent clinical signs of impending blast crisis were weakness, fatigue, increasing splenomegaly, anemia, thrombocytopenia, marrow fibrosis, and a rising neutrophil alkaline phosphatase. Fever (unrelated to infection), skin infiltration, lymphadenopathy, hepatomegaly, thrombocytosis, and basophilia were much less common. The development of aneuploidy occurred in less than one-half of the total group. Myeloblastic morphology at blastic transformation was most frequent with occasional lymphoblastic, promyelocytic, and undifferentiated cases seen. Terminal deoxynucleotidyl transferase was present in one-third of the patients, but had no clear-cut relationship to the morphology. Response to treatment was generally disappointing (two complete and 15 partial remissions in 45 treated patients).

Comparative evaluation of serum C-reactive protein levels in chronic and aggressive periodontitis patients and association with periodontal disease severity.

PubMed

Goyal, Lata; Bey, Afshan; Gupta, N D; Sharma, Vivek Kumar

2014-10-01

C-reactive protein (CRP) is an acute-phase reactant and has been proved to be a significant predictor of future cardiovascular events. Recent studies have demonstrated a correlation between periodontitis and elevated CRP levels. However, most of the studies have focused on chronic periodontitis and very few studies are done in patients with aggressive periodontitis. The aim of this study was to determine and compare the relative levels of serum CRP in aggressive and chronic periodontitis patients. A total of 75 systemically healthy subjects were divided into three groups: Group I, nonperiodontitis subjects; group II, chronic generalized periodontitis patients and group III, generalized aggressive periodontitis patients. All participants were subjected to quantitative CRP analysis using enzyme-linked immunosorbent assay. Mean CRP levels were significantly greater in both group II and III as compared to group I and group III having greater level than group II. Furthermore, CRP levels positively correlated with the amount of periodontal destruction as measured by probing depth and clinical attachment loss. The present study indicates a positive correlation between CRP and periodontal disease severity with particular concern in younger individuals that could be a possible underlying pathway in the association between periodontal disease and the observed higher risk for cardiovascular disease in periodontitis patients.

Simultaneous occurrence of t(9;22)(q34;q11.2) and t(16;16)(p13;q22) in a patient with chronic myeloid leukemia in blastic phase.

PubMed

Zámecníkova, Adriana; Al Bahar, Soad; Ramesh, Pandita

2008-06-01

Coexistence of two specific chromosomal translocations in the same clone is an infrequent phenomenon and has only rarely been reported in hematological malignancies. We report a combination of t(16;16)(p13;q22), the Philadelphia translocation t(9;22)(q34;q11.2), and deletion of the long arm of chromosome 7 in a patient with chronic myeloid leukemia in blast phase. Monotherapy treatment with imatinib mesylate resulted in the disappearance of the Ph-positive clone, but with persistence of t(16;16) and del(7) in all of the metaphases examined. The case illustrates that, although imatinib mesylate can be an effective treatment in eradication of the BCR-ABL fusion gene cells, the occurrence of additional specific abnormalities in Philadelphia-positive leukemias may pose a significant therapeutic challenge. (c) 2008 Elsevier Inc.

[A MODEL OF COMPREHENSIVE CARE FOR COMPLEX CHRONIC PATIENT. EXPERIENCE OF A TERRITORY].

PubMed

Torres, Montserrat; Fabrellas, Núria; Solà, Montserrat; Rubio Merchán, Antonia; Camañes Garcia, Neus; Berlanga, Sofía

2015-03-01

The Increase in life expectancy has brought an increase in chronic diseases. The evolution of chronic disease is the cause of several organic and systemic dysfunctions, leading to physical and mental limitations that determine the need for some aid to perform basic vital tasks. Primary health care has a key role in the monitoring of fragility, chronicity, and complexity of population. However, in order to address properly high complexity diseases it is necessary to know and coordinate the different resources existing inside the territory. THE DEVELOPMENT OF THE MODEL FOR ACTION: THE IMPLEMENTATIONS OF A FUNCTIONAL UNIT. The Primary Health Care must ensure equity, accessibility, longitudinally, and continuity of care, bearing in mind that health outcomes must be optimal. There are several health care providers in the Delta del Llobregat SAP, so it was implemented a strategic plan focused on the coordination and/or the reconciliation of all the devices involved in the assistance in order to provide comprehensive attention to the patient. The patients included in this program were to be identified as CCP (Complex chronic Patient), in an evolved and tributary phase of intensive follow-up. CONCLUSIONS. The identification ofpatients listed as CCP and at clinical risk allows a comprehensive monitoring in order to prevent exacerbations and overuse of unscheduled hospital resources.

Tinnitus school: an educational approach to tinnitus management based on a stress-reaction tinnitus model.

PubMed

Alpini, Dario; Cesarani, Antonio; Hahn, Ales

2007-01-01

Stress is a significant factor influencing the clinical course of tinnitus. The auditory system is particularly sensitive to the effects of various stress factors (chemical, oxidative, emotional, etc.). Different stages of reaction (alarm, resistance, exhaustion) lead to different characteristics of tinnitus and to different therapeutic approaches. Individual characteristics of stress reaction may explain different aspects of tinnitus in various patients with different responses to treatment, despite similar audiological and etiological factors. A model based on individual reactions to stress factors (stress-reaction tinnitus model, or SRTM) could explain tinnitus as an alarm signal. In each patient, stressors have to be identified during the alarm phase to prevent an evolution toward the resistance and exhaustion phases. In the exhaustion phase, chronic tinnitus is due to the organization of a paradoxical auditory memory and a pathologically shifted attention to tinnitus. The aim of our study is to describe a therapeutic proposal based on the SRTM by taking an educational approach to management of chronic tinnitus. The educational aspect is emphasized; thus, we named our approach tinnitus school. Selection of appropriate patients and follow-up is based on psychometrics of tinnitus and stress questionnaires, including a tinnitus reaction questionnaire, a tinnitus cognitive questionnaire, and a 20-item perceived stress questionnaire. Tinnitus school is a three-phase program: counseling, training, and home training. Training is based on a tinnitus-fitted physiotherapeutic protocol.

Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib.

PubMed

Swords, Ronan; Mahalingam, Devalingam; Padmanabhan, Swaminathan; Carew, Jennifer; Giles, Francis

2009-09-21

Chronic myeloid leukemia (CML) is the consequence of a single balanced translocation that produces the BCR-ABL fusion oncogene which is detectable in over 90% of patients at presentation. The BCR-ABL inhibitor imatinib mesylate (IM) has improved survival in all phases of CML and is the standard of care for newly diagnosed patients in chronic phase. Despite the very significant therapeutic benefits of IM, a small minority of patients with early stage disease do not benefit optimally while IM therapy in patients with advanced disease is of modest benefit in many. Diverse mechanisms may be responsible for IM failures, with point mutations within the Bcr-Abl kinase domain being amongst the most common resistance mechanisms described in patients with advanced CML. The development of novel agents designed to overcome IM resistance, while still primarily targeted on BCR-ABL, led to the creation of the high affinity aminopyrimidine inhibitor, nilotinib. Nilotinib is much more potent as a BCR-ABL inhibitor than IM and inhibits both wild type and IM-resistant BCR-ABL with significant clinical activity across the entire spectrum of BCR-ABL mutants with the exception of T315I. The selection of a second generation tyrosine kinase inhibitor to rescue patients with imatinib failure will be based on several factors including age, co-morbid medical problems and ABL kinase mutational profile. It should be noted that while the use of targeted BCR-ABL kinase inhibitors in CML represents a paradigm shift in CML management these agents are not likely to have activity against the quiescent CML stem cell pool. The purpose of this review is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior therapy with IM or dasatinib.

[The evaluation of patients with ischemic cerebral lesions by CT, SPECT and qEEG in acute, subacute and chronic phases].

PubMed

Sánchez-Chávez, J J; Barroso, E; Cubero, L; González-González, J; Farach, M

1998-08-01

SPECT, EEG AND CT scan offer information with several pathophysiologic meanings. Their results vary with time and according to the vascular affected territory. We wanted to study how the sensibility varies and the relationship with the clinic of SPECT, qEEG and CT scan in the acute, subacute and chronic stages and according to the vascular affected territory. We also wanted to analyze the several pathophysiologic aspects of the cerebral ischemia. Thirty-six patients with symptoms of hemispheric stroke were evaluated with CT scan, qEEG, SPECT99mTc-HMPAO during the acute (0-5 days), subacute (0-15 days) and chronic (16 days to 1 year) stages. The decrease of ipsilateral CBF depend on the time (p = 0.0061), being not very frequent during the two first weeks. The qEEG was the most sensitive study in the first phase, its sensibility did not depend on the vascular affected territory and was dependent on the time (p = 0.0011), diminishing in the chronic phase. The slow activity was habitually ipsilateral. The CT scan was the less sensitive study. After 24 hours and until the second week, there is habitually an increase of the ipsilateral rCBF. The luxury perfusion could explain the fogging effect in the CT scan. The slow activity of the qEEG represents the alteration of the oxygen metabolism. The interpretation of the variation of the CBF and the qEEG allow us to define oligemia of the ischemia and between reactive hyperemia and the increase of CBF due to the necrotic tissue.

At-Home Transcranial Direct Current Stimulation (tDCS) With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms

PubMed Central

Riggs, Alexa; Patel, Vaishali; Paneri, Bhaskar; Portenoy, Russell K.; Bikson, Marom; Knotkova, Helena

2018-01-01

Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications. Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support. Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS) and a tDCS user survey. Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10–20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients’ training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and there were no adverse events. Data collection was feasible and there were no missing data. Satisfaction with the tDCS-telehealth procedure was high and the patients were comfortable using the system. Conclusion: At-home tDCS with telehealth support appears to be a feasible approach for the management of symptom burden in patients with chronic illness. Further studies to evaluate and optimize the protocol effectiveness for symptom-control outcomes are warranted. PMID:29872381

A meta-analysis of placebo-controlled trials of omega-3 fatty acid augmentation in schizophrenia: Possible stage-specific effects.

PubMed

Chen, Alexander T; Chibnall, John T; Nasrallah, Henry A

2015-11-01

Omega-3 fatty acids have shown promise as an adjunctive treatment for schizophrenia. However, efficacy across studies has been inconsistent. We conducted a meta-analysis of published controlled studies with the goal of detecting different efficacy profiles at various stages of schizophrenia. An online search was conducted for randomized, double-blind, placebo-controlled clinical trials, and a meta-analysis was conducted. Ten studies met the criteria for inclusion. Among patients in the prodromal phase of schizophrenia, omega-3 supplementation reduced psychotic symptom severity and lowered conversion rates to first-episode psychosis. In patients with first-episode schizophrenia, omega-3 decreased nonpsychotic symptoms, required lower antipsychotic medication dosages, and improved early treatment response rates. Omega-3 had mixed results in patients with stable chronic schizophrenia, with only some patients experiencing significant benefits. Among patients with chronic schizophrenia, use of omega-3 fatty acids both by those experiencing acute exacerbations and those who had discontinued antipsychotic medications resulted in worsening of psychotic symptoms. The data suggest that omega-3 fatty acids may be efficacious in reducing clinical symptoms for patients in the earlier stages of schizophrenia (prodrome and first episode), while producing mixed results for patients in the chronic stages. Based on these results, omega-3 fatty acids would not be recommended for acute exacerbations in patients with chronic schizophrenia nor for relapse prevention after discontinuation of antipsychotics.

Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: Study design, methods and feasibility

PubMed Central

2006-01-01

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC. PMID:16848974

Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

ClinicalTrials.gov

2013-05-01

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study.

PubMed

Wang, Kevin K W; Yang, Zhihui; Yue, John K; Zhang, Zhiqun; Winkler, Ethan A; Puccio, Ava M; Diaz-Arrastia, Ramon; Lingsma, Hester F; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Gordon, Wayne A; Okonkwo, David O; Manley, Geoffrey T; Cooper, Shelly R; Dams-O'Connor, Kristen; Hricik, Allison J; Inoue, Tomoo; Maas, Andrew I R; Menon, David K; Schnyer, David M; Sinha, Tuhin K; Vassar, Mary J

2016-07-01

We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean ± standard error: 9.11 ± 1.42; n = 43) than healthy controls (2.90 ± 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 ± 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 ± 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 ± 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.

[Condition of neurohumoral regulation of bronchial tone and gallbladder in patients with chronic cholecystitis and chronic obstructive pulmonary disease].

PubMed

Dudka, T V; Khukhlina, O S; Dudka, I V

2014-01-01

SUMMARY The paper presents data from a study of the neuroendocrine regulation of nonstriated muscles, bronchial tree and the gallbladder tones by means of an assessment of the adrenergic and cholinergic systems state in patients, suffering from chronic obstructive pulmonary disease and chronic acalculous cholecystitis. Adrenergic and cholinergic activities as well as cortisol secretion have significantly changed. To study the features of adrenergic and cholinergic regulations of bronchial tone and that of the gallbladder in patients with combined course of chronic acalculous cholecystitis and chronic obstructive pulmonary disease. 92 patients were involved in the study: 30 patients with COPD (1st group), 30 patients with COPD of comorbid CAC in the acute phase (2nd group), 32 patients with CAC in the acute phase (3rd group) and a control group--30 practically healthy individuals (PHI) of the respective age. All the patients with COPD and COPD combined with CAC had a marked predominance of the parasympathetic nervous system, as evidenced by the established significant decrease of CDE (Table) in patients with isolated COPD is 1.4 times (p < 0.05), in patients with COPD combined with CAC--there was more intense inhibition of enzyme activity--in 1.8 times (p < 0.05) and in patients with CAC of the 3rd group there were identical changes--a decreased activity of CDE in 1.6 times (p < 0.05) with significant intergroup differences between the groups (p < 0.05). An analysis of the studies showed significant changes in the CDE of the surveyed individuals. For instance, the CDA in the individuals of groups 1 and 2 was lower by 1.6 and 2.4 times respectively (p < 0.001) than in the group of PHI; in the patients of the 3rd group--the changes were minor--a decline of 14.6% (p < 0.05) compared with practically healthy individuals (Table). Participation of sympathoadrenal system in the pathogenesis of COPD occurrence has been proved, however, in patients with COPD and CAC, the ability to deposit CA, when combined with CAC has significantly dropped. The study of cortisol density in the blood serum of the patients under examination showed its significant drop in all groups observed. For instance, the first group patients' blood contained 2.7 times (p < 0.05) less cortisol than that of PHI; in the patients of the second group the inhibition of the functional state of the adrenal cortex was even more intense--cortisol was lower than its index in the control group by 3.7 times (p < 0.05); the 3d group patients had the maximum drop in cortisol secretion by 1.7 times (p < 0.05) with reliable intergroup difference. The base of regulatory neuroendocrine and paracrine mecganisms imbalance, contributing to a development of COPD, is the cholinergic imbalance (reduction in blood acetylcholinesterase activity, hypertensive sphincter of Oddi dysfunction), adrenergic imbalance, reduction in catecholamine-depositing erythrocytes function, hypokinetic gallbladder dysfunction, adrenal dysfunction (decreased cortisol levels) that contribute to the development and progression of chronic cholecystitis against a background of hypokinetic gallbladder dysfunction.

Prevalence, incidence and clinical impact of cachexia: facts and numbers-update 2014.

PubMed

von Haehling, Stephan; Anker, Stefan D

2014-12-01

Cachexia is a serious but underrecognised consequence of many chronic diseases. Its prevalence ranges from 5-15 % in end-stage chronic heart failure to 50-80 % in advanced cancer. Cachexia is also part of the terminal course of many patients with chronic kidney disease, chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis. Mortality rates of patients with cachexia range from 10-15 % per year in COPD through 20-30 % per year in chronic heart failure and chronic kidney disease to 80 % in cancer. The condition is also associated with poor quality of life. In the industrialised world, the overall prevalence of cachexia (due to any disease and not necessarily associated with hospital admission) is growing and it currently affects around 1 % of the patient population, i.e. around 9 million people. It is also a significant health problem in other parts of the globe. Recently there have been advances in our understanding of the multifactorial nature of the condition, and particularly of the role of inflammatory mediators and the imbalance of anabolism and catabolism. Several promising approaches to treatment have failed to live up to the challenge of phase III clinical trials, but the ghrelin receptor agonist anamorelin seems to have fulfilled at least some early promise. Further advances are urgently needed.

Dopaminergic sensitivity and cocaine abuse: response to apomorphine.

PubMed

Hollander, E; Nunes, E; DeCaria, C M; Quitkin, F M; Cooper, T; Wager, S; Klein, D F

1990-08-01

Ten male patients with chronic cocaine abuse received a single dose of the dopamine agonist apomorphine. Self-ratings of cocaine craving, depression, and anxiety decreased in response to apomorphine. Neuroendocrine response was consistent with central dopaminergic stimulation. Patients in the "craving" phase of the cocaine abuse cycle differed in behavioral but not neuroendocrine response to apomorphine from patients in the "crash" phase. Decrease in cocaine craving correlated with decrease in plasma homovanillic acid (pHVA). Total cocaine consumption correlated negatively with baseline prolactin and pHVA levels and inversely with peak change in prolactin following apomorphine. Patients had blunted neuroendocrine response to apomorphine in comparison to historical normal controls. Implications for the "dopamine" hypothesis of cocaine abuse are discussed.

EEG Delta Band as a Marker of Brain Damage in Aphasic Patients after Recovery of Language

ERIC Educational Resources Information Center

Spironelli, Chiara; Angrilli, Alessandro

2009-01-01

In this study spectral delta percentage was used to assess both brain dysfunction/inhibition and functional linguistic impairment during different phases of word processing. To this aim, EEG delta amplitude was measured in 17 chronic non-fluent aphasic patients while engaged in three linguistic tasks: Orthographic, Phonological and Semantic.…

Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

ClinicalTrials.gov

2018-03-28

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression

PubMed Central

Beer, Philip A.; Knapp, David J. H. F.; Miller, Paul H.; Kannan, Nagarajan; Sloma, Ivan; Heel, Kathy; Babovic, Sonja; Bulaeva, Elizabeth; Rabu, Gabrielle; Terry, Jefferson; Druker, Brian J.; Loriaux, Marc M.; Loeb, Keith R.; Radich, Jerald P.; Erber, Wendy N.

2015-01-01

Without effective therapy, chronic-phase chronic myeloid leukemia (CP-CML) evolves into an acute leukemia (blast crisis [BC]) that displays either myeloid or B-lymphoid characteristics. This transition is often preceded by a clinically recognized, but biologically poorly characterized, accelerated phase (AP). Here, we report that IKAROS protein is absent or reduced in bone marrow blasts from most CML patients with advanced myeloid disease (AP or BC). This contrasts with primitive CP-CML cells and BCR-ABL1–negative acute myeloid leukemia blasts, which express readily detectable IKAROS. To investigate whether loss of IKAROS contributes to myeloid disease progression in CP-CML, we examined the effects of forced expression of a dominant-negative isoform of IKAROS (IK6) in CP-CML patients’ CD34+ cells. We confirmed that IK6 disrupts IKAROS activity in transduced CP-CML cells and showed that it confers on them features of AP-CML, including a prolonged increased output in vitro and in xenografted mice of primitive cells with an enhanced ability to differentiate into basophils. Expression of IK6 in CD34+ CP-CML cells also led to activation of signal transducer and activator of transcription 5 and transcriptional repression of its negative regulators. These findings implicate loss of IKAROS as a frequent step and potential diagnostic harbinger of progressive myeloid disease in CML patients. PMID:25370416

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

PubMed

Steegmann, Juan Luis; Colomer, Dolors; Gómez-Casares, Maria-Teresa; García-Gutiérrez, Valentín; Ortí, Guillermo; Ramírez-Payer, Angel; Olavarria, Eduardo; Vall-Llovera, Ferrán; Giraldo, Pilar; Conde, Eulogio; Vallansot, Rolando; López-Lorenzo, Jose Luis; Palomera, Luis; Álvarez-Larrán, Alberto; Conesa, Venancio; Bautista, Guiomar; Casas, Laura; Giles, Frank; Hochhaus, Andreas; Casado-Montero, Luis Felipe

2017-10-01

This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

BCR-ABL1 transcript at 3 months predicts long-term outcomes following second generation tyrosine kinase inhibitor therapy in the patients with chronic myeloid leukaemia in chronic phase who failed Imatinib.

PubMed

Kim, Dennis D; Lee, Honggi; Kamel-Reid, Suzanne; Lipton, Jeffrey H

2013-03-01

The BCR-ABL1 transcript level at 3 months can predict long-term outcomes following frontline therapy with Imatinib or Dasatinib in chronic myeloid leukaemia (CML) patients. However, data is lacking for second-generation tyrosine kinase inhibitor (2GTKI) therapy after Imatinib failure. A total of 112 patients with CML in chronic phase receiving 2GTKI after Imatinib failure were reviewed. Treatment outcomes including complete cytogenetic (CCyR), major molecular (MMR) and molecular response 4.5 (4.5 log reduction of BCR-ABL1 transcript level, MR(4.5) ), treatment failure, progression-free and overall survival (OS) were compared according to BCR-ABL1 transcript levels at 3 or 6 months, divided into <1%(IS) , 1-10%(IS) and ≥ 10%(IS) . BCR-ABL1 transcript level at 3 months showed better correlation with OS (P < 0.001) than that at 6 months (P = 0.147). Better OS was also observed in the patients achieving <1%(IS) (100%) and 1-10%(IS) (100%) than those with ≥ 10%(IS) at 3 months (70.6%, P < 0.001). Those with <1%(IS) showed the best CCyR, MMR and MR(4.5) rates; 1-10%(IS) , intermediate; and ≥ 10%(IS) , the lowest CCyR, MMR and MR(4.5) rates. The group with <1%(IS) at 3 months maintained significantly lower BCR-ABL1 transcript level compared to other two groups. In conclusion, the BCR-ABL1 transcript level at 3 months is the most relevant surrogate for outcomes following 2GTKI therapy after Imatinib failure. © 2012 Blackwell Publishing Ltd.

Development of the Andalusian Registry of Patients Receiving Community Case Management, for the follow-up of people with complex chronic diseases.

PubMed

Morales-Asencio, Jose M; Kaknani-Uttumchandani, Shakira; Cuevas-Fernández-Gallego, Magdalena; Palacios-Gómez, Leopoldo; Gutiérrez-Sequera, José L; Silvano-Arranz, Agustina; Batres-Sicilia, Juan Pedro; Delgado-Romero, Ascensión; Cejudo-Lopez, Ángela; Trabado-Herrera, Manuel; García-Lara, Esteban L; Martin-Santos, Francisco J; Morilla-Herrera, Juan C

2015-10-01

Complex chronic diseases are a challenge for the current configuration of health services. Case management is a service frequently provided for people with chronic conditions, and despite its effectiveness in many outcomes, such as mortality or readmissions, uncertainty remains about the most effective form of team organization, structures and the nature of the interventions. Many processes and outcomes of case management for people with complex chronic conditions cannot be addressed with the information provided by electronic clinical records. Registries are frequently used to deal with this weakness. The aim of this study was to generate a registry-based information system of patients receiving case management to identify their clinical characteristics, their context of care, events identified during their follow-up, interventions developed by case managers and services used. The study was divided into three phases, covering the detection of information needs, the design and its implementation in the health care system, using literature review and expert consensus methods to select variables that would be included in the registry. A total of 102 variables representing structure, processes and outcomes of case management were selected for their inclusion in the registry after the consensus phase. A web-based registry with modular and layered architecture was designed. The framework follows a pattern based on the model-view-controller approach. In its first 6 months after the implementation, 102 case managers have introduced an average number of 6.49 patients each one. The registry permits a complete and in-depth analysis of the characteristics of the patients who receive case management, the interventions delivered and some major outcomes as mortality, readmissions or adverse events. © 2015 John Wiley & Sons, Ltd.

Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients: a phase II randomized controlled trial.

PubMed

Michielsen, Marian E; Selles, Ruud W; van der Geest, Jos N; Eckhardt, Martine; Yavuzer, Gunes; Stam, Henk J; Smits, Marion; Ribbers, Gerard M; Bussmann, Johannes B J

2011-01-01

To evaluate for any clinical effects of home-based mirror therapy and subsequent cortical reorganization in patients with chronic stroke with moderate upper extremity paresis. A total of 40 chronic stroke patients (mean time post .onset, 3.9 years) were randomly assigned to the mirror group (n = 20) or the control group (n = 20) and then joined a 6-week training program. Both groups trained once a week under supervision of a physiotherapist at the rehabilitation center and practiced at home 1 hour daily, 5 times a week. The primary outcome measure was the Fugl-Meyer motor assessment (FMA). The grip force, spasticity, pain, dexterity, hand-use in daily life, and quality of life at baseline-posttreatment and at 6 months-were all measured by a blinded assessor. Changes in neural activation patterns were assessed with functional magnetic resonance imaging (fMRI) at baseline and posttreatment in an available subgroup (mirror, 12; control, 9). Posttreatment, the FMA improved more in the mirror than in the control group (3.6 ± 1.5, P < .05), but this improvement did not persist at follow-up. No changes were found on the other outcome measures (all Ps >.05). fMRI results showed a shift in activation balance within the primary motor cortex toward the affected hemisphere in the mirror group only (weighted laterality index difference 0.40 ± 0.39, P < .05). This phase II trial showed some effectiveness for mirror therapy in chronic stroke patients and is the first to associate mirror therapy with cortical reorganization. Future research has to determine the optimum practice intensity and duration for improvements to persist and generalize to other functional domains.

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib.

PubMed

Lee, Chung-Shien; Rattu, Mohammad A; Kim, Sara S

2016-02-01

Ibrutinib, a Bruton's kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory mantle cell lymphoma and subsequently for the treatment of relapsed refractory chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate in patients who received ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs. 4% in ofatumumab) and a significantly improved overall survival at 12 months (90% ibrutinib vs. 81% ofatumumab). Similar clinical benefits were shown regardless of del (17 p). Ibrutinib was well tolerated, and dose-limiting toxicity was not observed. Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid malignancies. Ibrutinib, as a monotherapy, is an effective treatment modality as a salvage therapy for treatment of mantle cell lymphoma and chronic lymphocytic leukemia / small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive chemotherapy and/or those with del (17 p). In patients with chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront therapy and/or as a combination therapy in indolent B-cell lymphoid malignancies. © The Author(s) 2014.

Barriers to participation in a phase II cardiac rehabilitation programme.

PubMed

Mak, Y M W; Chan, W K; Yue, C S S

2005-12-01

To identify barriers to participation in a phase II cardiac rehabilitation programme and measures that may enhance participation. Prospective study. Regional hospital, Hong Kong. Cardiac patients recruited for a phase I cardiac rehabilitation programme from July 2002 to January 2003. Reasons for not participating in a phase II cardiac rehabilitation programme. Of the 193 patients recruited for a phase I cardiac rehabilitation programme, 152 (79%) patients, with a mean age of 70.3 years (standard deviation, 11.9 years), did not proceed to phase II programme. Eleven (7%) deaths occurred before commencement of phase II and 74 (49%) patients were considered physically unfit. Reasons for the latter included fractures, pain, or degenerative changes in the lower limbs (24%), and co-morbidities such as cerebrovascular accident (19%), chronic renal failure (11%), congestive heart failure (9%), and unstable angina (8%). Phase II rehabilitation was postponed until after completion of scheduled cardiac interventions in 13% of patients. Failure of physicians to arrange the pre-phase II exercise stress test as per protocol was reported in 7% of patients. Other reasons were reported: work or time conflicts (16%), non-compliance with cardiac treatment (5%), financial constraints (4%), self-exercise (3%), fear after exercise stress testing (3%), and patients returning to their original cardiologists for treatment (3%). A significant (79%) proportion of patients did not proceed to a phase II cardiac rehabilitation programme for a variety of reasons. These included physical unfitness, work or time conflicts, and need to attend scheduled cardiac interventions. Further studies are required to determine how to overcome obstacles to cardiac rehabilitation.

Cortisol and hypothalamic–pituitary–gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

PubMed Central

Gur, Ali; Cevik, Remzi; Nas, Kemal; Colpan, Leyla; Sarac, Serdar

2004-01-01

We investigated abnormalities of the hypothalamic–pituitary–gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated – 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic–pituitary–gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations. PMID:15142269

Obinutuzumab Plus Chlorambucil for Patients with Chronic Lymphocytic Leukemia and Comorbidities

Cancer.gov

A summary of results from an international phase III trial that compared the combination of obinutuzumab (Gazyva™) and chlorambucil (Leukeran®) versus chlorambucil alone, as well as obinutuzumab plus chlorambucil versus rituximab (Rituxan®) plus chloramb

Directed use of the internet for health information by patients with chronic kidney disease: prospective cohort study.

PubMed

Diamantidis, Clarissa Jonas; Fink, Wanda; Yang, Shiming; Zuckerman, Marni R; Ginsberg, Jennifer; Hu, Peter; Xiao, Yan; Fink, Jeffrey C

2013-11-15

Health information technology has become common in the care of patients with chronic diseases; however, there are few such applications employed in kidney disease. The aim of the study was to evaluate the use of a website providing disease-specific safety information by patients with predialysis chronic kidney disease. As part of the Safe Kidney Care (SKC) study, an educational website was designed to provide information on safety concerns in chronic kidney disease. Phase I study participants were provided a medical alert accessory with a unique ID number, the Safe Kidney Care website, and an in-person tutorial on the use of the Internet and accessing the SKC website at baseline. Participants were asked to visit the website and enter their unique ID as frequently as they desired over the next 365 days or until their annual follow-up visit, whichever occurred first. Participants' visits and dwell times on specific safety modules were tracked using embedded webpage PHP scripts linked to a MySQL database, enabling the collection of website usage statistics. Of 108 Phase I participants, 28.7% (31/108) visited the website from 1-6 times during the observation period (median follow-up 365 days). Median access time was 7 minutes per visit (range <1-46) and 13 minutes per person (range <1-123). The three most frequently visited pages were "Renal function calculator", "Pills to avoid", and "Foods to avoid". High school education and frequent Internet use were significantly associated with website entry (P=.02 and P=.03, respectively). Preliminary results show general interest in a Web-based platform designed to improve patient safety in chronic kidney disease. Clinicaltrials.gov NCT01407367; http://clinicaltrials.gov/show/NCT01407367 (Archived by WebCite at http://www.webcitation.org/6KvxFKA6M).

Stage 1 development of a patient-reported experience measure (PREM) for chronic obstructive pulmonary disease (COPD).

PubMed

Walker, Susan; Andrew, Sharon; Hodson, Matthew; Roberts, C Michael

2017-07-24

The study aimed to explore patients' experience of living with chronic obstructive pulmonary disease and their perspective of their community healthcare for chronic obstructive pulmonary disease to extract affective responses in order to develop potential items for a patient-reported experience measure for chronic obstructive pulmonary disease. Qualitative face-face interviews were conducted, in the community, with 64 patients with chronic obstructive pulmonary disease recruited from General Practices and Breathe-Easy community groups in the Outer North East, East and City areas of London and Essex, UK. A two phase analysis of the qualitative data was conducted to identify themes arising from patients' description of living with chronic obstructive pulmonary disease and their perceptions of their community healthcare and subsequently the affective responses underlying the themes raised by patients, which gave emotional colour to the themes, bringing the thematic analysis closer to the subjective patient experience. Five themes were identified from the interview data: 'Journey to diagnosis'; 'Smoking'; 'Usual care'; 'My everyday life'; and 'Exacerbations'. Twenty-one affective responses were identified and categorised as either 'negative', 'positive' or 'bivalent'. 'Frustration', a negative affective response was prevalent in four themes. 'Gratitude', 'hope' and 'happiness/enjoyment' were among the more positive responses more prevalent across several themes. By conducting a novel two-way analysis (thematic and affective) it was possible to identify themes and affective responses that were aligned to those themes. This enabled the development of 38 chronic obstructive pulmonary disease-specific experience items to take forward for further testing including item reduction and validity and reliability in the next stage of the patient-reported experience measure development. GIVING IMPORTANCE TO PATIENTS' EMOTIONS: An exploration of patient perceptions of living with chronic lung disease will help develop a new patient reported experience scale. Healthcare services are aiming to provide effective patient-centered care for those with chronic obstructive pulmonary disease (COPD). Such care strategies require structured, validated patient feedback scales to facilitate accurate communication between patients, carers and healthcare professionals. Susan Walker at Anglia Ruskin University in Chelmsford, UK, and co-workers analyzed qualitative data from interviews with 64 COPD patients in London and Essex regarding their emotions and perceptions of living with COPD, with the aim of creating a patient reported experience measure, or PREM. Initial results identified five themes-including 'journey to diagnosis' and 'everyday life'-and twenty-one affective responses, ranging from negative to positive. The team will take these results forward for further validation.

[Introduction of disease management programmes in Germany as reflected by differing interests of health insurance companies and the federal association of statutory health insurance physicians].

PubMed

Erler, A

2002-11-01

On 1st January 2002 a law was enacted by the German Federal Government reorganising the reinsurance pool known as the "risk compensation scheme" (RSA) of the German health insurance system. This enactment contemplates a gradual restructuring of the RSA to shift from a system that considered only certain demographic criteria to one that reflects actual morbidity rates, with the shift to be phased in before full implementation by 2007. The enactment also introduced disease management programmes (DMP) for patients with certain chronic illnesses. Insurance companies will now receive additional payments from the RSA for patients with a chronic condition who are enrolled in a DMP. The intent is to improve the poor medical care for chronically ill patients in Germany - as had been stated by the advisory council of the Concerted Action in Health Care - and to reduce the natural tendency of insurance companies to prefer young healthy members over chronically ill patients. Possible consequences of the legal changes are discussed from the point of view of the various insurance companies as well as the Federal Association of Statutory Health Insurance Physicians.

Quality of life and depression in a cohort of female patients with chronic disease.

PubMed

Cardin, Fabrizio; Ambrosio, Francesco; Amodio, Piero; Minazzato, Lina; Bombonato, Giancarlo; Schiff, Sami; Finotti, Katiuscia; Giuliani, Daria; Bianco, Tonino; Terranova, Claudio; Militello, Carmelo; Ori, Carlo

2012-01-01

Differences in health-related quality of life perception in patients with chronic disease may depend on pre-existing differences in personality profile. The purpose of the study was to investigate in a cohort of female patients with chronic diseases the relationship between the Quality of Life perception and the potential presence of depressive symptoms. Female patients with chronic diseases were enrolled in the study. Exclusion criteria were diagnosis of psychopathological condition, treatment with psychoactive substances.Methodological approach was based on administration of the following test. Short Form health survey SF-36, Symptom Check List SCL-90-R, Satisfaction Profile test (SAT-P) and Beck Depression Inventory-II (BDI-II). The Pearson correlation coefficient was used to evaluate the relationship between depressive symptoms and Quality of life as assessed by psychometric test. 57 patients, aged 52(± 3,4), responded to inclusion criteria. 57% of patients had a diagnosis of functional dyspepsia or gastro-oesophageal reflux not complicated, and the remaining 43% musculoskeletal diseases. The statistical analysis showed an inverse correlation between the variable Bodily Pain of the SF-36 and the variable Depression scales of the SCL-90-R.In a second phase another sample of female patients was enrolled in the study. 64 patients, aged 49(± 3,2), responded to inclusion criteria.Another significant negative correlation was found between the Somatic-Affective factor of the BDI-II and the scale Physical Functioning of the SAT-P. In female patients with chronic disease depressive symptoms resulted influenced by pain and vice versa. The treatment of depressive symptoms could improve the quality of life of patients.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

PubMed Central

Hummer, Tom A.; Vohs, Jenifer L.; Yung, Matthew G.; Liffick, Emily; Mehdiyoun, Nicole F.; Radnovich, Alexander J.; McDonald, Brenna C.; Saykin, Andrew J.; Breier, Alan

2015-01-01

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n=35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness. PMID:25749917

Nociceptor Sensitization Depends on Age and Pain Chronicity123

PubMed Central

Dodge, Amanda K.

2016-01-01

Abstract Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID:26866058

Reduced tyrosine kinase inhibitor dose is predicted to be as effective as standard dose in chronic myeloid leukemia: A simulation study based on phase 3 trial data.

PubMed

Fassoni, Artur C; Baldow, Christoph; Roeder, Ingo; Glauche, Ingmar

2018-06-28

Continuing tyrosine kinase inhibitor mediated targeting of the BCR-ABL1 oncoprotein is the standard therapy for chronic myeloid leukemia and allows for a sustained disease control in the majority of patients. While therapy cessation for patients appeared as a safe option for about half of the optimally responding patients, a systematic assessment of long-term tyrosine kinase inhibitor dose de-escalation is missing. We use a mathematical model to analyze and consistently describe biphasic treatment responses from tyrosine kinase inhibitor treated patients from two independent clinical phase-3 trials. Scale estimates reveal that drug efficiency determines the initial response while the long-term behavior is limited by the rare activation of leukemic stem cells. We use this mathematical framework to investigate the influence of different dosing regimens on the treatment outcome. We provide strong evidence suggesting that tyrosine kinase inhibitor dose de-escalation (at least 50%) does not lead to a reduction of long-term treatment efficiency for most patients, which have already achieved sustained remission, and maintains the secondary decline of BCR-ABL1 levels. We demonstrate that continuous BCR-ABL1 monitoring provides patient-specific predictions of an optimal reduced dose not decreasing the anti-leukemic effect on residual leukemic stem cells. Our results are consistent with the interim results of the DESTINY trial and provide clinically testable predictions. Our results suggest that dose halving should be considered as a long-term treatment option for well-responding chronic myeloid leukemia patients under continuing maintenance therapy with tyrosine kinase inhibitors. We emphasize the clinical potential of this approach to reduce treatment-related side-effects and therapy costs. Copyright © 2018, Ferrata Storti Foundation.

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

PubMed

Morgia, Giuseppe; Russo, Giorgio Ivan; Urzì, Daniele; Privitera, Salvatore; Castelli, Tommaso; Favilla, Vincenzo; Cimino, Sebastiano

2017-06-30

The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies with greater sample size.

The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes.

PubMed

Loomba, R; Rivera, M M; McBurney, R; Park, Y; Haynes-Williams, V; Rehermann, B; Alter, H J; Herrine, S K; Liang, T J; Hoofnagle, J H; Heller, T

2011-03-01

Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. To establish natural history and complications of treatment of acute hepatitis C. Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects. Published 2010. This article is a US Government work and is in the public domain in the USA.

Correlation between ultrafiltration rate and phase angle measured by BIA in chronic kidney disease patients on regular hemodialysis

NASA Astrophysics Data System (ADS)

Nasution, B. R.; Lubis, A. R.

2018-03-01

Chronic Kidney Disease (CKD) patients with regular hemodialysis have high rates of morbidity and mortality that may be related to the hemodynamic effects of rapid UFR and low PhA value. In this study, we investigated whether high UFR is associated with a low value of PhA thus indirectly affect the risk of morbidity and mortality. UFR and Bioelectrical Impedance Analysis (BIA) examination on 92 subjects were recorded shortly after HD and analyzed by using Pearson correlation test. Multivariate analysis was also conducted to identify several factors that can affect the value of Phase angle. The number of HD regular CKD patients with PhA<4 based on the division of the UFR (cc/kg/h) <10, 10-13, ≥ 13, respectively were3, 10 and 6, whereas patients with ≥ 4 PhA <10, 10-13, ≥ 13respectively were 60, 11, and 2. The results showed a significant relationship between UFR with PhA. In CKD patients with regular HD, UFR has aninverse relationship with the value of PhA. After multivariate analysis, the UFR and the etiology of HD are still significantly affect the value of PhA. UFR optimal value in patients with CKD with regular HD is <10 cc/kg/h.

Quantitative phase imaging of platelets in patients with chronic renal failure treated with hemodialysis

NASA Astrophysics Data System (ADS)

Vasilenko, Irina; Vlasova, Elizaveta; Metelin, Vladislav; Kardasheva, Ziver

2018-02-01

The development of robust non-invasive laboratory screening methods for early diagnosis on the out-patient basis seems quite relevant for practical medicine. It is known, that platelet is an original biosensor, a detector of early changes in hemostasis condition. The aim of this study was to assess a potential of the quantitative phase imaging (QPI) technique for real time evaluation the influence of low-molecular weight and unfractionated heparin on platelets in patients with the end-stage of chronic renal failure, who were treated with program hemodialysis (PHD). The main group consisted of 21 patients who were administered a low-molecular weight heparin for hypocoagulation during the procedure of hemodialysis. The control group (15 patients) received unfractionated heparin. Morphodensitometric state of living platelets we evaluated by QPI using computer phase-interference microscope MIM (Moscow, Russia). We analyzed the optical-geometrical parameters and the morphological features of living platelets which reflected the degree of their activation at the beginning of PHD (before administration of heparin), in 15 minutes after it and at the end of the procedure. The results allow us to conclude that the use of low-molecular weight heparin provides better ratio of efficacy/safety and causes a reduction of the platelet activation during the hemodialysis procedure. Practical implementation of QPI for clinical monitoring of platelets makes it possible to obtain important information on hemostasis cell. It opens new opportunities to assess the efficacy of treatment, as well as for early diagnosis of complications for disease.

[ANMCO Position paper: Recommendations for the follow-up of patients with pulmonary thromboembolism].

PubMed

D'Agostino, Carlo; Zonzin, Pietro; Enea, Iolanda; Gulizia, Michele Massimo; Ageno, Walter; Agostoni, Piergiuseppe; Azzarito, Michele; Becattini, Cecilia; Bongarzoni, Amedeo; Bux, Francesca; Casazza, Franco; Corrieri, Nicoletta; D'Alto, Michele; D'Amato, Nicola; D'Armini, Andrea Maria; De Natale, Maria Grazia; Di Minno, Giovanni; Favretto, Giuseppe; Filippi, Lucia; Grazioli, Valentina; Palareti, Gualtiero; Pesavento, Raffaele; Roncon, Loris; Scelsi, Laura; Tufano, Antonella

2016-09-01

Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is the third most common cause of cardiovascular death. The management of the acute phase of VTE is well described in several papers and guidelines, whereas the management of the follow-up of the patients affected from VTE is less defined. This position paper of the Italian Association of Hospital Cardiologists (ANMCO) tries to fill the gap using currently available evidence and the opinion of the experts to suggest the most useful way to manage patients in the chronic phase.The clinical and laboratory tests acquired during the acute phase of the disease drives the decision of the following period. Acquired or congenital thrombophilic factors may be identified to explain an apparently not provoked VTE. In some patients, a not yet clinically evident cancer could be the trigger of VTE and this could lead to a different strategy. The main target of the post-acute management is to prevent relapse of the disease and to identify those patients who could worsen or develop chronic thromboembolic pulmonary hypertension. The knowledge of the etiopathogenetic ground is important to address the therapeutic approach, choosing the best antithrombotic strategy and deciding how long therapy should last. During the follow-up period, prognostic stratification should be updated on the basis of new evidences eventually acquired.Treatment of VTE is mainly based on oral or parenteral anticoagulation. Oral direct inhibitors of coagulation represent an interesting new therapy for the acute and extended period of treatment.

Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease.

PubMed

Galati, J S; Holdeman, K P; Dalrymple, G V; Harrison, K A; Quigley, E M

1994-05-01

To evaluate gastric emptying in patients with chronic liver disease and portal hypertension. We measured gastric emptying of both the liquid and solid components of a meal in 10 consecutive patients with chronic liver disease and portal hypertension, but free of ascites, and 14 age- and sex-matched healthy controls. In the patients with liver disease, relationships between emptying and liver function were examined. To measure gastric emptying, subjects consumed a test meal that consisted of scrambled eggs labeled with 99mTc-sulfur colloid and 4 oz of water labeled with 111In-diethylene triamine pentacetic acid (DTPA). Patients with liver disease and portal hypertension demonstrated delayed emptying of both the liquid (t1/2, min, mean +/- SE, patients vs. 69.4 +/- 19.4 vs. 31.4 +/- 1.8, p < 0.01) and solid (post-lag phase solid emptying: 141 +/- 32.9 vs. 69.8 +/- 4.6, p < 0.006) components of the meal. We could not identify any correlation between gastric emptying and tests of liver function. Gastric emptying is delayed in patients with liver disease and portal hypertension; this abnormal gastric motor function may contribute to the pathophysiology of foregut complaints in this patient population.

Split lesions of the peroneus brevis tendon in chronic ankle laxity.

PubMed

Bonnin, M; Tavernier, T; Bouysset, M

1997-01-01

Between 1993 and 1995, we operated on 18 patients for split lesions of the peroneal brevis tendon associated with chronic ankle instability. Five patients were competitive athletes, seven were recreational athletes, and six were persons. Symptoms developed in three phases: ankle sprain, chronic instability, and posterolateral pain. The mean delay between sprain and posterolateral pain was 6 years. At the time of surgery the main complaint was retromalleolar pain in nine patients, pain and instability in eight patients, and instability only in one patient. Diagnosis of tendinous lesions was based on clinical examination in three cases, preoperative magnetic resonance imaging in eight cases, preoperative tenography in one case, and surgical exploration in six cases. The lesion was localized at the tip of the lateral malleolus and was visible only after opening the peroneal retinaculum. In three cases an accessory peroneal muscle was present. A Chrisman-Snook procedure was performed in 13 cases and a simple tendinous repair in 5 cases. The split lesion of the peroneus brevis tendon may be the result of chronic ankle laxity. This lesion needs a specific surgical treatment and the peroneal tendon must be checked in case of surgical procedure for ankle laxity. After ligamentous repair, residual pain can be due to a neglected peroneus brevis tear.

Impact of exclusion criteria for the DASISION and ENESTnd trials in the front-line treatment of a 'real-life' patient population with chronic myeloid leukaemia.

PubMed

Latagliata, Roberto; Carmosino, Ida; Vozella, Federico; Volpicelli, Paola; De Angelis, Federico; Loglisci, Maria Giovanna; Salaroli, Adriano; De Luca, Maria Lucia; Montagna, Chiara; Serrao, Alessandra; Molica, Matteo; Diverio, Daniela; Nanni, Mauro; Mancini, Marco; Breccia, Massimo; Alimena, Giuliana

2017-06-01

Both Dasision and ENESTnd trials had many exclusion criteria, with a possible selection bias compared with the real-life. To address the impact of this bias on the first-line treatment in the current clinical practice, we revised 207 unselected newly diagnosed chronic phase chronic myeloid leukaemia (CML) patients [M/F 108/99, median age 58.8 years, interquartile range 42.3-70.2] treated with front-line imatinib from June 2002 to June 2013 at our Institution, and evaluated how many of them would have been excluded from enrolment in the two trials. Twenty-eight patients (13.5%) should have been excluded by both trials because of polycomorbidities (12), severe cardiomyopathy (five), age > 80 with frailty (three), drug abuse (two) or other severe concomitant diseases (six). In addition, eight patients should have been excluded by Dasision due to isolated chronic obstructive broncopulmonar disease, and 19 patients should have been excluded by ENESTnd due to isolated diabetes (10), arrhythmia (four), acute myocardial infarction > 6 months before CML diagnosis (two), chronic pancreatic disease (two) and peripheral arterial obstructive disease (one). On the whole, 36 patients (17.4%) would have been excluded by Dasision trial and 47 (22.7%) by ENESTnd trial. The patients potentially not eligible for both trials were significantly older and with imatinib had a worse outcome compared with patients potentially eligible. Our data highlight that an automatic transposition of results available in clinical controlled trials into the frontline real-life management of CML patients should be regarded with caution. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Efficacy, Safety, and Tolerability of Fulranumab as an Adjunctive Therapy in Patients With Inadequately Controlled, Moderate-to-Severe Chronic Low Back Pain: A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Dose-loading Phase II Study.

PubMed

Sanga, Panna; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Thipphawong, John

2016-06-01

Fulranumab is an investigational, fully human recombinant monoclonal antibody (IgG2) that neutralizes the biological actions of human nerve growth factor. Low back pain is a common cause of noncancer chronic pain and represents one of the most significant socioeconomic health-related problems in developed countries. This randomized, double-blind, placebo-controlled study was conducted to evaluate the analgesic effect of fulranumab in patients with moderate-to-severe chronic low back pain. Patients (aged 18-80 years) were randomized to receive subcutaneous injections every 4 weeks in 1 of 5 parallel treatment groups: placebo or fulranumab 1mg (1mgQ4wk), 3mg (3mgQ4wk), 3mg after a 6mg loading dose (6mgLD+3mgQ4wk), or 10mg (10mgQ4wk) every 4 weeks. A total of 385 patients (median age, 53 years; women, 54%) received at least 1 injection of study medication. No statistically significant differences were observed in improvement of pain intensity scores between the fulranumab treatment regimens and the placebo group at week 12 (primary end point; mean [SD], placebo: -2.0 [2.17], 1mgQ4wk: -1.9 [2.14], 3mgQ4wk: -2.2 [1.89], 6mgLD+3mgQ4wk: -2.0 [1.72] and 10mgQ4wk: -2.1 [2.18]). Results for secondary efficacy parameters (change in the Oswestry Disability Index, Brief Pain Inventory-Short Form, and Patient Global Assessment scales) were consistent with the primary outcome. A placebo effect was observed; the overall percentage of patients with treatment-emergent adverse events (TEAEs) was similar between the placebo (76%) and fulranumab treatment groups (77%-90%). Across all phases, the most common TEAEs in at least 10% of patients (combined fulranumab group vs placebo) were arthralgia (15% vs 12%), back pain (15% vs 18%), upper respiratory tract infection (15% vs 8%), paresthesia (14% vs 8%), diarrhea (12% vs 4%), headache (12% vs 8%), hypoesthesia (11% vs 5%), pain in extremity (11% vs 8%), sinusitis (10% vs 5%), and nasopharyngitis (10% vs 9%). Across all phases, neurologic TEAEs were less frequent in the placebo group (14%) versus the fulranumab treatment groups (25%). In the posttreatment phase, 8 patients had joint replacement operations, which were considered a result of normal progression of osteoarthritis. One case in the 10-mg group was determined to be rapid progession of osteoarthritis and was considered to be possibly related to study drug. Fulranumab did not demonstrate efficacy compared with placebo in patients with chronic low back pain but was generally well-tolerated. ClinicalTrials.gov identifier: NCT00973024. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study.

PubMed

Bussel, James B; de Miguel, Purificación Garcia; Despotovic, Jenny M; Grainger, John D; Sevilla, Julián; Blanchette, Victor S; Krishnamurti, Lakshmanan; Connor, Philip; David, Michèle; Boayue, Koh B; Matthews, Dana C; Lambert, Michele P; Marcello, Lisa M; Iyengar, Malini; Chan, Geoffrey W; Chagin, Karen D; Theodore, Dickens; Bailey, Christine K; Bakshi, Kalpana K

2015-08-01

The oral thrombopoietin receptor agonist eltrombopag is approved for treatment of adults with chronic immune thrombocytopenia. In the PETIT trial, we aimed to investigate the efficacy and safety of eltrombopag in children with persistent or chronic immune thrombocytopenia. PETIT was a three-part, randomised, multicentre, placebo-controlled study done at 22 centres in the USA, UK, Canada, Spain, France, and the Netherlands. Patients aged 1-17 years with immune thrombocytopenia lasting for 6 months or longer and platelets less than 30 × 10(9) per L who had received at least one previous treatment were enrolled. We enrolled patients into three cohorts consisting of patients aged 12-17, 6-11, and 1-5 years. We established patients' starting doses with an open-label, dose-finding phase with five patients in each cohort. During the dose-finding phase, patients aged 6-17 years started eltrombopag at 25 mg once per day (12·5 mg for those weighing <27 kg) and patients aged 1-5 years received 0·7 mg/kg per day to a maximum of 2 mg/kg unless otherwise approved. We permitted dose adjustments on the basis of platelet response up to a maximum dosage of 75 mg per day. Additional patients were then recruited and randomly assigned (2:1) to receive either eltrombopag or placebo tablets (or oral suspension formulation if aged 1-5 years) once per day for 7 weeks at the previously established doses. Starting doses for the double-blind phase were 37·5 mg/day for patients aged 12-17 years; 50 mg/day for patients weighing 27 kg or more (25 mg for east Asian patients) and 25 mg/day for patients weighing less than 27 kg (12·5 mg once per day for east Asian patients) for patients aged 6-11 years; and 1·5 mg/kg once per day (0·8 mg/kg once per day for east Asian patients) for patients aged 1-5 years. Randomisation was done by the GlaxoSmithKline Registration/Medication Ordering System and both patients and study personnel were masked to treatment assignments. Patients who completed treatment were then enrolled into an open-label phase and all patients could receive up to 24 weeks of eltrombopag. The primary outcome was the proportion of patients achieving a platelet count of 50 × 10(9) per L or more at least once from weeks 1-6 (days 8 to 43) of the randomised phase of the study in the absence of rescue therapy. We assessed efficacy in the intent-to-treat population, which consisted of all patients assigned to treatment, and we assessed safety in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT00908037. Between Oct 2, 2009, and June 22, 2011, we recruited 15 patients, with five patients in each age cohort, into the open-label dose-finding phase who did not progress into the double-blind phase. From March 17, 2010, to Jan 15, 2013, we randomly assigned 67 patients to treatment, with 45 patients assigned to receive eltrombopag (16 children aged 12-17 years, 19 aged 6-11 years, and ten aged 1-5 years) and 22 to receive placebo (eight children aged 12-17 years, nine aged 6-11 years, and five aged 1-5 years). However, two patients assigned to receive eltrombopag did not receive the study drug and one was lost to follow-up, and one patient assigned to receive placebo was given eltrombopag. From weeks 1 to 6, 28 (62%) patients who received eltrombopag, compared with seven (32%) who received placebo, achieved the primary endpoint of platelet count 50 × 10(9) per L or more at least once without rescue (odds ratio 4·31, 95% CI 1·39-13·34, p=0·011). The most common adverse events with eltrombopag were headache (13 [30%] patients receiving eltrombopag vs nine [43%] patients receiving placebo), upper respiratory tract infection (11 [25%] patients vs two [10%] patients), and diarrhoea (seven [16%] patients vs one [5%] patient). Grade 3 or 4 adverse events occurred in five (11%) patients receiving eltrombopag and four (19%) patients receiving placebo, and serious adverse events (four [9%] patients receiving eltrombopag and two (10%) patients receiving placebo) were similarly infrequent in both groups. No thrombotic events or malignancies occurred. Increased alanine aminotransferase concentrations caused two (3%) of 65 patients to discontinue eltrombopag in the open-label phase. Our results showed that eltrombopag could be used to increase platelet counts and reduce clinically significant bleeding in children with persistent or chronic immune thrombocytopenia. Prevalence of increased liver laboratory values was similar to that seen in adults. GlaxoSmithKline. Copyright © 2015 Elsevier Ltd. All rights reserved.

Applying disease management strategies to Medicare.

PubMed

Tompkins, C P; Bhalotra, S; Trisolini, M; Wallack, S S; Rasgon, S; Yeoh, H

1999-01-01

Medicare coverage begins for many when they have already developed one or more chronic diseases, and it often pays for the latest and costliest phases. Population-based disease modeling, patient screening, and monitoring would be appropriate interventions for chronic renal disease. Patients who have not yet advanced to end-stage renal disease would benefit from management of diabetes and hypertension, avoidance of nephrotoxic substances, and better preparation for dialysis. Administrative support could take the form of clinical guidelines, physician-led multidisciplinary teams, integrated delivery systems, provider and patient education, and new information technologies. Medicare reflects the long-term public perspective, and thus should further this new direction by supporting education, reimbursing for prevention efforts and allied health services, encouraging efficiency, and monitoring cost and quality outcomes.

Changes in Gait Symmetry After Training on a Treadmill with Biofeedback in Chronic Stroke Patients: A 6-Month Follow-Up from a Randomized Controlled Trial

PubMed Central

Drużbicki, Mariusz; Guzik, Agnieszka; Przysada, Grzegorz; Kwolek, Andrzej; Brzozowska-Magoń, Agnieszka; Sobolewski, Marek

2016-01-01

Background One of the most significant challenges for patients who survive a stroke is relearning basic motor tasks such as walking. The goal of this study was to evaluate whether training on a treadmill with visual biofeedback improves gait symmetry, as well as spatiotemporal and kinematic gait parameters, in stroke patients. Material/Methods Thirty patients in the chronic phase after a stroke were randomly allocated into groups with a rehabilitation program of treadmill training with or without visual biofeedback. The training program lasted 10 days. Spatiotemporal and kinematic gait parameters were evaluated. For all parameters analyzed, a symmetrical index was calculated. Follow-up studies were performed 6 months after completion of the program. Results The symmetrical index had significantly normalized in terms of the step length (p=0.006), stance phase time, and inter-limb ratio in the intervention group. After 6 months, the improvement in the symmetry of the step length had been maintained. In the control group, no statistically significant change was observed in any of the parameters tested. There was no significant difference between the intervention group and the control group on completion of the program or at 6 months following the completion of the program. Conclusions Training on a treadmill has a significant effect on the improvement of spatiotemporal parameters and symmetry of gait in patients with chronic stroke. In the group with the treadmill training using visual biofeedback, no significantly greater improvement was observed. PMID:27941712

Rehabilitation needs and participation restriction in patients with cognitive disorder in the chronic phase of traumatic brain injury

PubMed Central

Sashika, Hironobu; Takada, Kaoruko; Kikuchi, Naohisa

2017-01-01

Abstract The purpose of this study was to clarify psychosocial factors/problems, social participation, quality of life (QOL), and rehabilitation needs in chronic-phase traumatic brain injury (TBI) patients with cognitive disorder discharged from the level-1 trauma center (L1-TC), and to inspect the effects of rehabilitation intervention to these subjects. A mixed-method research (cross-sectional and qualitative study) was conducted at an outpatient rehabilitation department. Inclusion criteria of subjects were transfer to the L1-TC due to TBI; acute-stage rehabilitation treatment received in the L1-TC from November 2006 to October 2011; age of ≥18 and <70 years at the time of injury; a score of 0–3 on the Modified Rankin Scale at discharge and that of 4–5 due to physical or severe aggressive behavioral comorbid disorders. Study details were sent, via mail, to 84 suitable candidates, of whom 36 replied. Thirty-one subjects (median age: 33.4 years; male: 17; and average time since injury: 48.1 months), who had consented to study participation, were participated. Cognitive function, social participation, QOL, psychosocial factors/problems, rehabilitation needs, and chronic-phase rehabilitation outcomes were evaluated using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, the Zung Self-Rating Depression Scale, the Sydney Psychosocial Reintegration Scale, Version 2, and the Short Form 36, Version 2, qualitative analysis of semistructured interviews, etc. Participants were classified into achieved-social-participation (n = 11; employed: 8), difficult-social-participation (n = 12; unemployed: 8), and no-cognitive-dysfunction groups (n = 8; no social participation restriction). Relative to the achieved-social-participation group, the difficult-social-participation group showed greater injury and cognitive dysfunction and lower Sydney Psychosocial Reintegration Scale and Short Form 36 role/social component summary scores (64.9/49.1 vs 44.3/30.4, respectively, P < 0.05). Linear regression analysis showed that the social participation status was greatly affected by the later cognitive disorders and psychosocial factors/problems not by the severity of TBI. No changes were observed in these scores following chronic-phase rehabilitation intervention. Chronic-phase TBI with cognitive disorder led to rehabilitation needs, and improvement of subjects’ psychosocial problems and QOL was difficult. PMID:28121947

Rehabilitation needs and participation restriction in patients with cognitive disorder in the chronic phase of traumatic brain injury.

PubMed

Sashika, Hironobu; Takada, Kaoruko; Kikuchi, Naohisa

2017-01-01

The purpose of this study was to clarify psychosocial factors/problems, social participation, quality of life (QOL), and rehabilitation needs in chronic-phase traumatic brain injury (TBI) patients with cognitive disorder discharged from the level-1 trauma center (L1-TC), and to inspect the effects of rehabilitation intervention to these subjects.A mixed-method research (cross-sectional and qualitative study) was conducted at an outpatient rehabilitation department.Inclusion criteria of subjects were transfer to the L1-TC due to TBI; acute-stage rehabilitation treatment received in the L1-TC from November 2006 to October 2011; age of ≥18 and <70 years at the time of injury; a score of 0-3 on the Modified Rankin Scale at discharge and that of 4-5 due to physical or severe aggressive behavioral comorbid disorders. Study details were sent, via mail, to 84 suitable candidates, of whom 36 replied. Thirty-one subjects (median age: 33.4 years; male: 17; and average time since injury: 48.1 months), who had consented to study participation, were participated. Cognitive function, social participation, QOL, psychosocial factors/problems, rehabilitation needs, and chronic-phase rehabilitation outcomes were evaluated using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, the Zung Self-Rating Depression Scale, the Sydney Psychosocial Reintegration Scale, Version 2, and the Short Form 36, Version 2, qualitative analysis of semistructured interviews, etc.Participants were classified into achieved-social-participation (n = 11; employed: 8), difficult-social-participation (n = 12; unemployed: 8), and no-cognitive-dysfunction groups (n = 8; no social participation restriction). Relative to the achieved-social-participation group, the difficult-social-participation group showed greater injury and cognitive dysfunction and lower Sydney Psychosocial Reintegration Scale and Short Form 36 role/social component summary scores (64.9/49.1 vs 44.3/30.4, respectively, P < 0.05). Linear regression analysis showed that the social participation status was greatly affected by the later cognitive disorders and psychosocial factors/problems not by the severity of TBI. No changes were observed in these scores following chronic-phase rehabilitation intervention.Chronic-phase TBI with cognitive disorder led to rehabilitation needs, and improvement of subjects' psychosocial problems and QOL was difficult.

Dyspnea, chest wall hyperinflation, and rib cage distortion in exercising patients with chronic obstructive pulmonary disease.

PubMed

Bruni, Giulia Innocenti; Gigliotti, Francesco; Binazzi, Barbara; Romagnoli, Isabella; Duranti, Roberto; Scano, Giorgio

2012-06-01

Whether dyspnea, chest wall dynamic hyperinflation, and abnormalities of rib cage motion are interrelated phenomena has not been systematically evaluated in patients with chronic obstructive pulmonary disease (COPD). Our hypothesis that they are not interrelated was based on the following observations: (i) externally imposed expiratory flow limitation is associated with no rib cage distortion during strenuous incremental exercise, with indexes of hyperinflation not being correlated with dyspnea, and (ii) end-expiratory chest wall volume may either increase or decrease during exercise in patients with COPD, with those who hyperinflate being as breathless as those who do not. Sixteen patients breathed either room air or 50% supplemental O2 at 75% of peak exercise in randomized order. We evaluated the volume of chest wall (V(cw)) and its compartments: the upper rib cage (V(rcp)), lower rib cage (V(rca)), and abdomen (V(ab)) using optoelectronic plethysmography; rib cage distortion was assessed by measuring the phase angle shift between V(rcp) and V(rca). Ten patients increased end-expiratory V(cw) (V(cw,ee)) on air. In seven hyperinflators and three non-hyperinflators, the lower rib cage paradoxed inward during inspiration with a phase angle of 63.4° ± 30.7° compared with a normal phase angle of 16.1° ± 2.3° recorded in patients without rib cage distortion. Dyspnea (by Borg scale) averaged 8.2 and 9 at the end of exercise on air in patients with and without rib cage distortion, respectively. At iso-time during exercise with oxygen, decreased dyspnea was associated with a decrease in ventilation regardless of whether patients distorted the rib cage, dynamically hyperinflated, or deflated the chest wall. Dyspnea, chest wall dynamic hyperinflation, and rib cage distortion are not interrelated phenomena.

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein.

PubMed

Ahn, Jem Ma; Paik, Yong-Han; Lee, Jun Hee; Cho, Ju Yeon; Sohn, Won; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2015-12-01

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.

Polarization-phase diagnostics of latent course of cholelithiasis in patients with chronic cholecystitis combined with diabetes mellitus type 2

NASA Astrophysics Data System (ADS)

Fediv, O. I.; Ivashchuk, O. I.; Marchuk, Yu. F.; Andriychuk, D. R.

2011-09-01

The principles of optical model of human bile polycrystalline structure are described. The three optical levels - isotropic, liquid-crystal and solid-crystal have been proposed. It has been introduced and proposed the scenarios of phase distribution formation in the boundary field of laser radiation, transformed by bile layers. The experimental scheme of direct measurement of coordinate phase distributions has been presented. The results of investigating the interrelation between the values of correlation and fractal parameters are presented. They characterize the coordinate distributions of phase shifts between the orthogonal components of the amplitude in the points of laser images of bile smears of cholelithiasis patients in combination with other pathologies. The diagnostic criteria of the cholelithiasis nascency and its severity degree differentiation are determined.

Venetoclax for the treatment of patients with chronic lymphocytic leukemia.

PubMed

Crombie, Jennifer; Davids, Matthew S

2017-06-01

Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp up and close tumor lysis syndrome monitoring and prophylaxis. Other toxicities, such as neutropenia and gastrointestinal adverse events, were manageable. Venetoclax monotherapy resulted in durable and deep responses in patients with relapsed, refractory CLL, including for those with deletion 17p, leading to the approval of venetoclax by the US FDA for relapsed or refractory deletion 17p CLL, and recently to additional approvals in Europe and Canada. Trials also suggest that venetoclax induces deeper and more durable responses when used in combination with rituximab, and combination studies with other agents are ongoing. Phase III trials are also underway, and will provide data on the efficacy and safety of venetoclax in combination with monoclonal antibodies and targeted therapies in larger patient populations.

A mobile application improves therapy-adherence rates in elderly patients undergoing rehabilitation

PubMed Central

Mertens, Alexander; Brandl, Christopher; Miron-Shatz, Talya; Schlick, Christopher; Neumann, Till; Kribben, Andreas; Meister, Sven; Diamantidis, Clarissa Jonas; Albrecht, Urs-Vito; Horn, Peter; Becker, Stefan

2016-01-01

Abstract Medication adherence is crucial for success in the management of patients with chronic conditions. This study analyzes whether a mobile application on a tablet aimed at supporting drug intake and vital sign parameter documentation affects adherence in elderly patients. Patients with coronary heart disease and no prior knowledge of tablet computers were recruited. They received a personal introduction to the mobile application Medication Plan, installed on an Apple iPad. The study was conducted using a crossover design with 3 sequences: initial phase, interventional phase (28 days of using the app system), and comparative phase (28 days of using a paper diary). Users experienced the interventional and comparative phases alternately. A total of 24 patients (12 males; mean age 73.8 years) were enrolled in the study. The mean for subjectively assessed adherence (A14-scale; 5-point Likert scale, from “never” to “very often” which results in a score from 0 to 56) before the study was 50.0 (SD = 3.44). After both interventions there was a significant increase, which was more pronounced after the interventional phase (54.0; SD = 2.01) than after the comparative phase (52.6; SD = 2.49) (for all pairs after both interventions, P <0.001). Neither medical conditions nor the number of drug intake (amount and frequency of drug taking) per day affected subjective adherence. Logging data showed a significantly stronger adherence for the medication app than the paper system for both blood pressure recordings (P <0.001) and medication intake (P = 0.033). The majority of participants (n = 22) stated that they would like to use the medication app in their daily lives and would not need further assistance with the app. A mobile app for medication adherence increased objectively and subjectively measured adherence in elderly users undergoing rehabilitation. The findings have promising clinical implications: digital tools can assist chronic disease patients achieve adherence to medication and to blood pressure measurement. Although this requires initial offline training, it can reduce complications and clinical overload because of nonadherence. PMID:27603339

A Web-Based Decision Tool to Improve Contraceptive Counseling for Women With Chronic Medical Conditions: Protocol For a Mixed Methods Implementation Study.

PubMed

Wu, Justine P; Damschroder, Laura J; Fetters, Michael D; Zikmund-Fisher, Brian J; Crabtree, Benjamin F; Hudson, Shawna V; Ruffin, Mack T; Fucinari, Juliana; Kang, Minji; Taichman, L Susan; Creswell, John W

2018-04-18

Women with chronic medical conditions, such as diabetes and hypertension, have a higher risk of pregnancy-related complications compared with women without medical conditions and should be offered contraception if desired. Although evidence based guidelines for contraceptive selection in the presence of medical conditions are available via the United States Medical Eligibility Criteria (US MEC), these guidelines are underutilized. Research also supports the use of decision tools to promote shared decision making between patients and providers during contraceptive counseling. The overall goal of the MiHealth, MiChoice project is to design and implement a theory-driven, Web-based tool that incorporates the US MEC (provider-level intervention) within the vehicle of a contraceptive decision tool for women with chronic medical conditions (patient-level intervention) in community-based primary care settings (practice-level intervention). This will be a 3-phase study that includes a predesign phase, a design phase, and a testing phase in a randomized controlled trial. This study protocol describes phase 1 and aim 1, which is to determine patient-, provider-, and practice-level factors that are relevant to the design and implementation of the contraceptive decision tool. This is a mixed methods implementation study. To customize the delivery of the US MEC in the decision tool, we selected high-priority constructs from the Consolidated Framework for Implementation Research and the Theoretical Domains Framework to drive data collection and analysis at the practice and provider level, respectively. A conceptual model that incorporates constructs from the transtheoretical model and the health beliefs model undergirds patient-level data collection and analysis and will inform customization of the decision tool for this population. We will recruit 6 community-based primary care practices and conduct quantitative surveys and semistructured qualitative interviews with women who have chronic medical conditions, their primary care providers (PCPs), and clinic staff, as well as field observations of practice activities. Quantitative survey data will be summarized with simple descriptive statistics and relationships between participant characteristics and contraceptive recommendations (for PCPs), and current contraceptive use (for patients) will be examined using Fisher exact test. We will conduct thematic analysis of qualitative data from interviews and field observations. The integration of data will occur by comparing, contrasting, and synthesizing qualitative and quantitative findings to inform the future development and implementation of the intervention. We are currently enrolling practices and anticipate study completion in 15 months. This protocol describes the first phase of a multiphase mixed methods study to develop and implement a Web-based decision tool that is customized to meet the needs of women with chronic medical conditions in primary care settings. Study findings will promote contraceptive counseling via shared decision making and reflect evidence-based guidelines for contraceptive selection. ClinicalTrials.gov NCT03153644; https://clinicaltrials.gov/ct2/show/NCT03153644 (Archived by WebCite at http://www.webcitation.org/6yUkA5lK8). ©Justine P Wu, Laura J Damschroder, Michael D Fetters, Brian J Zikmund-Fisher, Benjamin F Crabtree, Shawna V Hudson, Mack T Ruffin IV, Juliana Fucinari, Minji Kang, L Susan Taichman, John W Creswell. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.04.2018.

Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia.

PubMed

Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Albano, Francesco; Iurlo, Alessandra; Intermesoli, Tamara; Abruzzese, Elisabetta; Levato, Luciano; D'Adda, Mariella; Pregno, Patrizia; Cavazzini, Francesco; Stagno, Fabio; Martino, Bruno; La Barba, Gaetano; Sorà, Federica; Tiribelli, Mario; Bigazzi, Catia; Binotto, Gianni; Bonifacio, Massimiliano; Caracciolo, Clementina; Soverini, Simona; Foà, Robin; Cavo, Michele; Martinelli, Giovanni; Pane, Fabrizio; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

2017-09-01

The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials in which imatinib was given as first-line treatment. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow-up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to diagnosis of the second primary malignancies was 34 months. We did not find a higher incidence of second primary malignancies compared to that in the age- and sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% CI: 0.57-1.54) and 1.61 (95% CI: 0.92-2.31) in males and females, respectively. Overall, 3.1% patients died of second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to that expected in the age- and sex-matched Italian population, with a standardized mortality ratio of 2.41 (95% CI: 1.26 - 3.56). In conclusion, our analysis of patients with imatinib-treated chronic myeloid leukemia did not reveal a higher incidence of second primary malignancies; however, the outcome of second primary malignancies in such patients was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926. Copyright© 2017 Ferrata Storti Foundation.

The cortisol level and its relationship with depression, stress and anxiety indices in chronic methamphetamine-dependent patients and normal individuals undergoing inguinal hernia surgery.

PubMed

Pirnia, Bijan; Givi, Fatemeh; Roshan, Rasool; Pirnia, Kambiz; Soleimani, Ali Akbar

2016-01-01

Stimulants addition and abuse can cause some functional and morphological changes in the normal function of glands and hormones. Methamphetamine as an addictive stimulant drug affects the Hypothalamic- pituitary-adrenal (HPA) axis and consequently makes some changes in the psychological state of the drug users. The present study aims to examine the relationship between plasma levels of cortisol with depression, stress and anxiety symptoms in chronic methamphetamine-dependent patients and normal individuals who have undergone the inguinal hernia surgery. To meet the purpose of the study, 35 chronic methamphetamine-dependent patients in the active phase of drug abuse and 35 non-users (N=70) who were homogenized regarding the demographic features were purposefully selected from among the patients referred to undergo inguinal hernia surgery since March 15 to June 9, 2015. The participants were then divided into the control and experiment group. The changes in cortisol levels in plasma were measured using Radioimmunoassay (RIA) in three-time series including 0 (upon the induction of anesthesia), 12 and 24 hours after the surgery. Further, three behavioral indices of depression, anxiety and stress were measured using the Depression Anxiety Stress Scale 21 (DASS-21) and then the data were analyzed using t-test and Pearson Correlation coefficient. The plasma level of cortisol in the chronic methamphetamine-dependent patients (experiment group) had a significant increase in 24 hours after surgery (p<0.05). This study showed that cortisol levels in chronic methamphetamine-dependent patients were significantly higher than non-dependent patients in response to alarming events such as inguinal surgery. Changes in cortisol levels were intensified due to a confrontation with the phenomenon of pain and anxiety. In addition, depression index was higher in the chronic methamphetaminedependent patients than that in the non-dependent patients. However, there was no significant relationship between the cortisol level and depression index (p=0.001). The Hypothalamic-pituitary-adrenal (HPA) axis is considered as a key structure in the addiction to simulants, the reason which can explain the faster response of the chronic methamphetamine-dependent patients to the stressors such as surgery.

Comparative evaluation of serum C-reactive protein levels in chronic and aggressive periodontitis patients and association with periodontal disease severity

PubMed Central

Goyal, Lata; Bey, Afshan; Gupta, N. D.; Sharma, Vivek Kumar

2014-01-01

Objective: C-reactive protein (CRP) is an acute-phase reactant and has been proved to be a significant predictor of future cardiovascular events. Recent studies have demonstrated a correlation between periodontitis and elevated CRP levels. However, most of the studies have focused on chronic periodontitis and very few studies are done in patients with aggressive periodontitis. The aim of this study was to determine and compare the relative levels of serum CRP in aggressive and chronic periodontitis patients. Materials and Methods: A total of 75 systemically healthy subjects were divided into three groups: Group I, nonperiodontitis subjects; group II, chronic generalized periodontitis patients and group III, generalized aggressive periodontitis patients. All participants were subjected to quantitative CRP analysis using enzyme-linked immunosorbent assay. Results: Mean CRP levels were significantly greater in both group II and III as compared to group I and group III having greater level than group II. Furthermore, CRP levels positively correlated with the amount of periodontal destruction as measured by probing depth and clinical attachment loss. Conclusion: The present study indicates a positive correlation between CRP and periodontal disease severity with particular concern in younger individuals that could be a possible underlying pathway in the association between periodontal disease and the observed higher risk for cardiovascular disease in periodontitis patients. PMID:25395764

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.

PubMed

Khorshied, Mervat Mamdooh; Shaheen, Iman Abdel Mohsen; Abu Khalil, Reham E; Sheir, Rania Elsayed

2014-01-01

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib.

PubMed

Brümmendorf, Tim H; Cortes, Jorge E; Khoury, Hanna J; Kantarjian, Hagop M; Kim, Dong-Wook; Schafhausen, Philippe; Conlan, Maureen G; Shapiro, Mark; Turnbull, Kathleen; Leip, Eric; Gambacorti-Passerini, Carlo; Lipton, Jeff H

2016-01-01

The dual SRC/ABL1 tyrosine kinase inhibitor bosutinib is indicated for adults with Ph+ chronic myeloid leukaemia (CML) resistant/intolerant to prior therapy. This analysis of an ongoing phase 1/2 study (NCT00261846) assessed effects of baseline patient characteristics on long-term efficacy and safety of bosutinib 500 mg/day in adults with imatinib (IM)-resistant (IM-R; n = 196)/IM-intolerant (IM-I; n = 90) chronic phase (CP) CML. Median treatment duration was 24·8 months (median follow-up, 43·6 months). Cumulative major cytogenetic response (MCyR) rate [95% confidence interval (CI)], was 59% (53-65%); Kaplan-Meier (KM) probability of maintaining MCyR at 4 years was 75% (66-81%). Cumulative incidence of on-treatment progression/death at 4 years was 19% (95% CI, 15-24%); KM 2-year overall survival was 91% (87-94%). Significant baseline predictors of both MCyR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MCyR, prior interferon therapy and <6 months duration from diagnosis to IM treatment initiation and no interferon treatment before IM. The most common adverse event (AE) was diarrhoea (86%). Baseline bosutinib-sensitive BCR-ABL1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver-related AEs. Bosutinib demonstrates durable efficacy and manageable toxicity in IM-R/IM-I CP-CML patients. © 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Recent advances in pharmacological treatments of hyperkalemia: focus on patiromer.

PubMed

Epstein, Murray; Pitt, Bertram

2016-07-01

Hyperkalemia is a common electrolyte disorder, especially among patients with chronic kidney disease (CKD), diabetes mellitus, or heart failure, and is associated with a significantly increased risk for all-cause mortality. Hyperkalemia remains a vexing and challenging problem for clinicians, particularly in the management of patients with chronic kidney disease and congestive heart failure. Several observational and retrospective studies have reported a large gap between recommendations in guidelines and real-world practice in the implementation of RAASi therapies. RAASi treatment regimens are frequently down-titrated or discontinued following hyperkalemia events, with consequent worse outcomes than patients who remain on maximum doses. This review covers the preclinical and clinical studies that led to the approval of patiromer for the treatment of hyperkalemia. A literature search on patiromer was carried out using the PubMed database up to December 2015. Recently, patiromer was approved by the FDA as the first new potassium binder for the treatment of hyperkalemia in over 50 years. Based on the results of phase II and phase III studies, we conclude that patiromer is a well-tolerated and predictable medication to consistently and safely reduce serum potassium levels and to sustain normokalemia for periods up to 52 weeks in patients with diverse underlying diseases including congestive heart failure, and chronic kidney disease. Future research questions that should be evaluated are: the role of patiromer in treating hyperkalemia and the potential to thereby allow the optimal management of resistant hypertension and the use of high dose MRAs in patients with acute decompensated heart failure. Additional research is also warranted in the potential safety benefits of reducing potassium fluctuations in patients on hemodialysis as a result of treatment of hyperkalemia with patiromer.

A Phase II Trial of Fludarabine/Melphalan 100 Conditioning Therapy Followed by Allogeneic Hematopoietic Cell Transplantation for Patients With Lymphoma.

PubMed

Lee, Jung-Hee; Lee, Je-Hwan; Kim, Dae-Young; Seol, Miee; Lee, Young-Shin; Kang, Young-Ah; Jeon, Mijin; Lee, Kyoo-Hyung

2015-11-01

Conditioning therapy with fludarabine and melphalan 140 mg/m(2) has been widely used before allogeneic hematopoietic cell transplantation (HCT) for lymphoma. A lower dose of melphalan might result in lower mortality and morbidity without compromising engraftment. In our phase II trial, we investigated a conditioning regimen of fludarabine (30 mg/m(2)/day for 5 days on days -6 to -2) and melphalan (100 mg/m(2) on day -2). Antithymocyte globulin was added to fludarabine and melphalan for unrelated or mismatched familial donor HCT. The present study included 26 patients with lymphoma (B-cell in 10, T-cell in 11, and natural killer/T-cell lymphoma in 2). An objective tumor response after HCT was observed in 18 patients (75.0%; complete in 14 and partial in 4). Acute and chronic graft-versus-host disease (GVHD) occurred in 23.1% and 55.0% of the assessable patients, respectively. The 5-year overall survival, nonrelapse mortality, progression-free survival, and event-free survival rate was 40.4%, 21.6%, 39.2%, and 30.8%, respectively. Donor lymphocyte infusions were given to 3 patients who had developed a relapse or progression after HCT, and 2 of whom had a showed partial response. Patients with severe chronic GVHD had greater overall survival than those with no, mild, or moderate chronic GVHD. Conditioning therapy with a lower dose of melphalan, combined with fludarabine, appears to be promising in allogeneic HCT for lymphoma. The Clinicaltrials.gov identification number for the present study is NCT00772811. Copyright © 2015 Elsevier Inc. All rights reserved.

Phase IIa Study of the Immunogenicity and Safety of the Novel Staphylococcus aureus Vaccine V710 in Adults with End-Stage Renal Disease Receiving Hemodialysis

PubMed Central

Moustafa, Moustafa; Aronoff, George R.; Chandran, Chandra; Hartzel, Jonathan S.; Smugar, Steven S.; Galphin, Claude M.; Mailloux, Lionel U.; Brown, Elizabeth; DiNubile, Mark J.; Kartsonis, Nicholas A.

2012-01-01

Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 μg V710 (with or without adjuvant), 90 μg V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a ≥2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a ≥2.5 GMFR in anti-IsdB antibodies compared to the baseline (P values of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis. PMID:22837094

Development of a chronic kidney disease patient navigator program.

PubMed

Jolly, Stacey E; Navaneethan, Sankar D; Schold, Jesse D; Arrigain, Susana; Konig, Victoria; Burrucker, Yvette K; Hyland, Jennifer; Dann, Priscilla; Tucky, Barbara H; Sharp, John W; Nally, Joseph V

2015-05-03

Chronic Kidney Disease (CKD) is a public health problem and there is a scarcity of type 2 CKD translational research that incorporates educational tools. Patient navigators have been shown to be effective at reducing disparities and improving outcomes in the oncology field. We describe the creation of a CKD Patient Navigator program designed to help coordinate care, address system-barriers, and educate/motivate patients. The conceptual framework for the CKD Patient Navigator Program is rooted in the Chronic Care Model that has a main goal of high-quality chronic disease management. Our established multidisciplinary CKD research team enlisted new members from information technology and data management to help create the program. It encompassed three phases: hiring, training, and implementation. For hiring, we wanted a non-medical or lay person with a college degree that possessed strong interpersonal skills and experience in a service-orientated field. For training, there were three key areas: general patient navigator training, CKD education, and electronic health record (EHR) training. For implementation, we defined barriers of care and created EHR templates for which pertinent study data could be extracted. We have hired two CKD patient navigators who will be responsible for navigating CKD patients enrolled in a clinical trial. They have undergone training in general patient navigation, specific CKD education through directed readings and clinical shadowing, as well as EHR and other patient related privacy and research training. The need for novel approaches like our CKD patient navigator program designed to impact CKD care is vital and should utilize team-based care and health information technology given the changing landscape of our health systems.

Cutaneous myeloid sarcoma of the penile foreskin.

PubMed

Afrose, Ruquiya; Nebhnani, Deepa; Wadhwa, Neelam

2015-01-01

Myeloid sarcoma, considered to herald the onset of a blast crisis in the setting of chronic myeloproliferative neoplasm/dysplasia, typically presents during the course of the disorder. Cutaneous involvement is uncommon and lesions on genital skin are seldom seen. We present a case of a well-differentiated myeloid sarcoma in the penile foreskin in an apparently healthy 29-year-old male presenting with phimosis. The unusual composition of the inflammatory cell infiltrate, and characteristic sparing of dermal blood vessels, nerves and smooth muscle fibres led to the correct diagnosis. Absence of commonly observed changes in the circumcision skin like those of balanitis xerotica was also helpful. Detailed hematological work up revealed a previously undiagnosed chronic myeloid leukemia in chronic phase. The patient also had simultaneous priapism, another rare presentation of chronic myeloid leukemia. One year hence, the patient is in hematological remission with no evidence of extramedullary disease. Although priapism has been described as a rare presenting symptom in chronic myeloid leukemia, the present case is unique as this is the first time a cutaneous myeloid sarcoma has been documented in the penile foreskin.

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

Effect of scaling and root planing on erythrocyte count, hemoglobin and hematocrit in patients with chronic periodontal disease.

PubMed

Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Grover, Deepak; Kaur, Aaswin

2012-01-01

Anemia of chronic disease, a cytokine-mediated anemia, is a frequent complication of many chronic inflammatory conditions. The present clinical trial was aimed to evaluate the effect of chronic periodontal disease on erythrocyte count, hemoglobin and hematocrit and the changes produced in these parameters after the provision of periodontal therapy. 40 systemically healthy non-smoker male subjects in the age group of 25 to 50 years suffering with chronic periodontal disease were selected and categorized into 2 groups. Group A was categorized as chronic generalized gingivitis, and Group B was categorized as chronic generalized periodontitis on the basis of clinical findings. The clinical parameters Gingival Index (GI), Probing Pock et Depth (PPD) and Relative Attachment Level (RAL) and laboratory blood investigations viz erythrocyte count (EC), hemoglobin (Hb), hematocrit (HCT) and red cell indices (MCV, MCH, MCHC) were recorded at baseline. Complete oral prophylaxis was performed for all patients. Patients were recalled after 3 weeks and 3 months. The clinical and hematological parameters were re-evaluated to analyze the changes after provision of phase I therapy. The mean values of EC, Hb and HCT were significantly lower in Group B in comparison to Group A, and showed a significantly greater increase at 3 months of observation. However, the values of MCV, MCH and MCHC showed a non significant change during the same observation period in both the groups. Lower values of EC, Hb and HCT in Group B showed that mild anemia is associated with chronic generalized periodontitis, which tends to improve after provision of periodontal therapy. Minimal changes in MCV, MCH and MCHC indicated that the lower values are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease.

Quality of life of pulmonary TB patients after intensive phase treatmentin the health centers of Medan city, Indonesia

NASA Astrophysics Data System (ADS)

Wahyuni, A. S.; Soeroso, N.; Harahap, J.; Amelia, R.; Alona, I.

2018-03-01

Tuberculosis (TB) is one of the chronic diseases that has become a long major health problem in the world, as well as in Indonesia. TB treatment takes a long time (6-9 months) to cover both intensive and advanced phases. TB patients experience significant disruptions in their social life, exposed to stigma and discrimination. The purpose of this study was to determine the quality of life of TB patients after two months of TB intensive treatment phase. We conducted a quantitative study through cross-sectional design. This research recruited 100 TB patients aged > 18 years old and Category I with AFB(+) result. We involved patients from 7 Health Centers in Medan City. We utilised SF 36 instrument to assess the patients quality of lifein the interview. To analyse the collected data, we performed Independent t-analysis. The result of this study was that the quality of life of TB patients who had undergone initial treatment phase wasina low category with a score of 63.9. The two best-measured aspects of quality of life among the eight dimensions assessed in the instrument were pain and physical function.

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

PubMed Central

Barrientos, Jacqueline C.; Barr, Paul M.; Flinn, Ian W.; Burger, Jan A.; Tran, Anh; Clow, Fong; James, Danelle F.; Graef, Thorsten; Friedberg, Jonathan W.; Rai, Kanti; O’Brien, Susan

2015-01-01

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. PMID:25755291

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia.

PubMed

Brown, Jennifer R; Barrientos, Jacqueline C; Barr, Paul M; Flinn, Ian W; Burger, Jan A; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W; Rai, Kanti; O'Brien, Susan

2015-05-07

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. © 2015 by The American Society of Hematology.

Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors.

PubMed

Weir, Matthew R; Bakris, George L; Bushinsky, David A; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Wittes, Janet; Christ-Schmidt, Heidi; Berman, Lance; Pitt, Bertram

2015-01-15

Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial. Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase. In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was -1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%. In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK ClinicalTrials.gov number, NCT01810939.).

7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

ClinicalTrials.gov

2013-09-27

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Venetoclax in Patients with Previously Treated Chronic Lymphocytic Leukemia.

PubMed

Roberts, Andrew W; Stilgenbauer, Stephan; Seymour, John F; Huang, David C S

2017-08-15

Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacologic mimic of the proteins that initiate apoptosis (a so-called BH3 mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells, which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a phase I study, including complete remissions in 20% of patients. Its use was approved by the FDA in April 2016 for patients with previously treated del(17p) CLL on the basis of a single-arm phase II trial demonstrating a 79% response rate and an estimated 1-year progression-free survival of 72% with 400 mg/day continuous therapy. This review focuses on venetoclax, its mechanism of action, pharmacology, and clinical trial data and seeks to place it in the context of rapid advances in therapy for patients with relapsed CLL, especially those with del(17p) CLL. Clin Cancer Res; 23(16); 4527-33. ©2017 AACR . ©2017 American Association for Cancer Research.

[The role of expired air moisture condensate in assessment of pulmonary inflammation in patients with chronic obstructive pulmonary disease].

PubMed

Dotsenko, E K; Goncharova, V A; Kuzubova, N A; Kamenova, M Iu; Egorova, N V

2008-01-01

To study biochemical composition of expired air condensate (EAC) in patients with chronic obstructive pulmonary disease (COPD) in relation to a phase and severity of the disease and its treatment. EAC was investigated in 18 COPD patients and 9 healthy subjects. Basic broncholytic therapy with ipratropium bromide was combined with beclomethasone and fenspiride in 11 and 7 patients, respectively. The condensate was lyophilised, the residue was solved and analysed on the biochemical analyzer Casis (Beringer Manheim, Rosch). EAC was examined for albumin, C-reactive protein, glucose, cholesterol, triglycerides, urea, uric acid, alkaline phosphatase (AP), lactate dehydrogenase, gamma-glutamyl transferase, total calcium, magnesium. Compared to healthy subjects, COPD patients' EAC contains significantly higher levels of albumin, C-reactive protein, calcium, bilirubin and more active AP. Quantitative composition of EAC depends on COPD phase and severity. A negative correlation exists between FEV+AEA-1 and albumin concentration, FEV+AEA-1 and CRP concentration. The anti-inflammatory therapy decreases EAC content of both protein and lipid metabolism products, enzyme activity reflecting attenuation of oxidant and inflammatory processes, stabilization of cell membranes in the respiratory zone. EAC composition reflects metabolic processes in the lungs and can be used for assessment of airway affection, activity of the inflammatory process and COPD treatment efficacy.

Autobiographical memory and structural brain changes in chronic phase TBI.

PubMed

Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sofosbuvir, a Significant Paradigm Change in HCV Treatment

PubMed Central

McQuaid, Thomas; Savini, Carolyn; Seyedkazemi, Star

2015-01-01

Nucleotide compounds like sofosbuvir, acyclovir, and tenofovir have proven to be amongst the most potent orally available antiviral treatments. These drugs exhibit high efficacy and a wide therapeutic index, with demonstrated utility in a number of chronic viral infections. The approval of Sovaldi™, brand name for sofosbuvir, by the U.S. Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment. Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977. It was subsequently acquired and advanced through phase 3 development by Gilead Sciences, Inc. In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious. Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR), curing patients in excess of 80% in all genotypes and >90% in treatment-naïve subjects being administered combination therapy with other agents. Harvoni® is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet, and it has demonstrated high SVR rates in patients infected with HCV genotype 1, without the need for exogenous interferon and/or ribavirin. Here, we discuss the discovery, development, pharmacologic characterization, and results from the phase 3 trials of sofosbuvir. Hepatitis C is a chronic disease, for which most patients have been undiagnosed, are unwilling to start treatment, or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy. Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care, thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines. PMID:26357632

Chronic disease self-management: a hybrid concept analysis.

PubMed

Miller, Wendy R; Lasiter, Sue; Bartlett Ellis, Rebecca; Buelow, Janice M

2015-01-01

Chronic diseases require chronic disease self-management (CDSM). Existing CDSM interventions, while improving outcomes, often do not lead to long-lasting effects. To render existing and new CDSM interventions more effective, an exploration of the concept of CDSM from both the literature and patient perspectives is needed. The purpose of this study was to describe the current conceptualization of CDSM in the literature, identify potential inadequacies in this conceptualization based on a comparison of literature- and patient-based CDSM descriptions, and to offer a more comprehensive definition of CDSM. A hybrid concept analysis was completed. In the literature, CDSM is defined as behaviors influenced by individual characteristics. Patients in the fieldwork phase discussed aspects of CDSM not well represented in the literature. CDSM is a complex process involving behaviors at multiple levels of a person's environment. Pilot work to develop and test CDSM interventions based on both individual and external characteristics is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Using 2nd generation tyrosine kinase inhibitors in frontline management of chronic phase chronic myeloid leukemia

PubMed Central

Jayakar, Vishal

2014-01-01

Choices in medicine come with responsibility. With several TKI's (Tyrosine kinase inhibitors) available for front-line management of CML (Chronic Myeloid Leukemia), an astute clinician has to personalise, rationalise and take a pragmatic approach towards selection of the best drug for the ‘patient in question’. Though it is hotly debated as to which TKI will triumph, the truth of this debate lies in individualising treatment rather than a general ‘all size fits all’ approach with imatinib. I personally believe that the second generation TKI's will suit most patient clinical profiles rather than prescribing imatinib to all and I have strived to make a strong case for them in front line treatment of CML. Though Imatinib may remain the first line choice for some patients, my efforts in this debate are mainly geared towards breaking the myth that imatinib is the sole ‘block buster’ on the CML landscape PMID:24665456

Emerging therapies for the management of chronic hyperkalemia in the ambulatory care setting.

PubMed

Henneman, Amy; Guirguis, Erenie; Grace, Yasmin; Patel, Dimple; Shah, Bhoomi

2016-01-15

Emerging treatment options for the management of chronic hyperkalemia in the outpatient setting are reviewed. Current treatment options for the management of hyperkalemia are limited and often accompanied by serious adverse effects. Two investigational drugs for the treatment of hyperkalemia are being evaluated in Phase III trials: sodium zirconium cyclosilicate and patiromer. Both of these drugs are administered orally and act by enhancing potassium's removal, predominantly through the gastrointestinal tract. The safety and efficacy of sodium zirconium cyclosilicate and patiromer were evaluated in Phase II and III trials. Both agents were studied in patients with chronic mild-to-severe hyperkalemia, chronic kidney disease (CKD), or heart failure as well as those taking a renin-angiotensin system (RAS) inhibitor, an aldosterone antagonist, or both therapies. These clinical trials found that sodium zirconium cyclosilicate and patiromer normalized serum potassium levels quickly and maintained normalized serum potassium levels over several weeks. Both medications caused a rapid decrease in serum potassium, with two studies examining efficacy endpoints for 12 weeks or longer. The overall frequency of adverse effects in these clinical trials was low, with gastrointestinal adverse events being the most commonly observed. Options for the management of hyperkalemia, particularly chronic hyperkalemia in the outpatient setting, are limited. Both sodium zirconium cyclosilicate and patiromer are emerging therapies that may provide long-term management of hyperkalemia, particularly in patients with underlying heart failure or CKD as well as those taking an RAS inhibitor, an aldosterone antagonist, or both. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

[Update on the respiratory management of patients with chronic neuromuscular disease].

PubMed

Priou, P; Trzepizur, W; Meslier, N; Gagnadoux, F

2017-12-01

Neuromuscular diseases include a wide range of conditions that may involve potentially life-threatening respiratory complications (infection, respiratory failure). For patients with neuromuscular diseases, clinical assessment of respiratory function and regular pulmonary function tests are needed to screen for nocturnal respiratory disorders, weakness of the diaphragm and potential restrictive disorders and/or chronic hypercapnic respiratory insufficiency, possibly with couch deficiency. MANAGEMENT OF NOCTURNAL RESPIRATORY DISORDERS AND CHRONIC RESPIRATORY FAILURE: Nocturnal respiratory assistance is an important phase of care for nocturnal respiratory disorders and chronic respiratory failure. This may involve continuous positive airway pressure, adaptative servo-ventilation or non-invasive ventilation with a facial or nasal mask. As needed, diurnal assistance may be proposed by mouthpiece ventilation. Should non-invasive ventilation prove insufficient, or if significant swallowing disorders or recurrent bronchial obstruction develop, or in case of prolonged intubation, tracheotomy may be required. In case of lower airway infection with ineffective cough, physical therapy, associated with air stacking, intermittent positive pressure breathing or mechanical in-exsufflation may be proposed. Care for swallowing disorders, nutritional counseling (cachexia, obesity), vaccinations and therapeutic education are integral elements of patient-centered management aiming to prevent the negative impact of infection and to manage respiratory failure of chronic neuromuscular disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

PubMed

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-07-17

Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

PubMed Central

Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-01-01

Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0–10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results. PMID:28716797

Interferon alpha 2 maintenance therapy may enable high rates of treatment discontinuation in chronic myeloid leukemia.

PubMed

Burchert, A; Saussele, S; Eigendorff, E; Müller, M C; Sohlbach, K; Inselmann, S; Schütz, C; Metzelder, S K; Ziermann, J; Kostrewa, P; Hoffmann, J; Hehlmann, R; Neubauer, A; Hochhaus, A

2015-06-01

A minority of chronic myeloid leukemia (CML) patients is capable of successfully discontinuing imatinib. Treatment modalities to increase this proportion are currently unknown. Here, we assessed the role of interferon alpha 2a (IFN) on therapy discontinuation in a previously reported cohort of 20 chronic phase CML patients who were treated upfront with IFN alpha plus imatinib followed by IFN monotherapy to maintain cytogenetic or molecular remission (MR) after imatinib discontinuation. After a median follow-up of 7.9 years (range, 5.2-12.2), relapse-free survival was 73% (8/11 patients) and 84% (5/6 patients) for patients who discontinued imatinib in major MR (MMR) and MR4/MR4.5, respectively. Ten patients discontinued IFN after a median of 4.5 years (range, 0.24-9.3). After a median of 2.8 years (range, 0.7-5.1), nine of them remain in ongoing treatment-free remission with MR5 (n=6) and MR4.5 (n=3). The four patients who still administer IFN are in stable MR5, MR4.5, MR4, and MMR, respectively. In conclusion, an IFN/imatinib induction treatment followed by a temporary IFN maintenance therapy may enable a high rate of treatment discontinuation in CML patients in at least MMR when stopping imatinib.

Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion.

PubMed

Breccia, Massimo; Pregno, Patrizia; Spallarossa, Paolo; Arboscello, Eleonora; Ciceri, Fabio; Giorgi, Mauro; Grossi, Alberto; Mallardo, Mario; Nodari, Savina; Ottolini, Stefano; Sala, Carla; Tortorella, Giovanni; Rosti, Gianantonio; Pane, Fabrizio; Minotti, Giorgio; Baccarani, Michele

2017-04-01

Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia.

Long-lasting memory of cellular immunity in a chronic myeloid leukemia patient maintains molecular response 5 after cessation of dasatinib

PubMed Central

Jo, Tatsuro; Noguchi, Kazuhiro; Hayashi, Shizuka; Irie, Sadaharu; Hayase, Risa; Shioya, Haruna; Kaneko, Youhei; Horio, Kensuke; Taguchi, Jun

2018-01-01

Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2.4 years after stopping dasatinib was reported. Memory and effector CTLs and NK cells, were observed after 2.4 years of treatment-free remission, despite the fact that lymphocyte counts are not elevated in the patient. These results suggest that dasatinib may induce cellular immunity, including NK cells and CTLs and this cellular immunity may be maintained for a long period following cessation of dasatinib. The results suggest that this cellular immunity may provide a long-term cure without the need for continued TKI treatment. PMID:29435021

[Dysphagia management of acute and long-term critically ill intensive care patients].

PubMed

Zielske, J; Bohne, S; Axer, H; Brunkhorst, F M; Guntinas-Lichius, O

2014-10-01

Dysphagia is a severe complication in critically ill patients and affects more than half the patients in an intensive care unit. Dysphagia also has a strong impact on morbidity and mortality. Risk factors for the development of dysphagia are neurological diseases, age >55-70 years, intubation >7 days and sepsis. With increasing numbers of long-term survivors chronic dysphagia is becoming an increasing problem. There is not much knowledge on the influence of specific diseases, including the direct impact of sepsis on the development of dysphagia. Fiberoptic evaluation of swallowing is a standardized tool for bedside evaluation, helping to plan swallowing training during the acute phase and to decrease the rate of chronic dysphagia. For evaluation of chronic dysphagia even more extensive diagnostic tools as well as several options of stepwise rehabilitation using restitution, compensation and adaption strategies for swallowing exist. Currently it seems that these options are not being sufficiently utilized. In general, there is a need for controlled clinical trials analyzing specific swallowing rehabilitation concepts for former critically ill patients and long-term survivors.

Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease

ClinicalTrials.gov

2018-03-23

Acute Biphenotypic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Adult Acute Lymphoblastic Leukemia in Complete Remission; Aggressive Non-Hodgkin Lymphoma; Beta-2-Microglobulin Greater Than 3 g/mL; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; Chromosome 13 Abnormality; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Lymphoblastic Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome With Excess Blasts; Myelofibrosis; Pancytopenia; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma

Comparative analysis of gingival crevicular fluid β-glucuronidase levels in health, chronic gingivitis and chronic periodontitis.

PubMed

Sanara, P P; Shereef, Mohammed; Hegde, Shashikanth; Rajesh, K S; Arun Kumar, M S; Mohamed, Shabeer

2015-08-01

Current methods available for periodontal disease diagnosis are seriously deficient in terms of accuracy, in the ability to predict ongoing or future disease activity and indeed in determining whether previously diseased sites are in an arrested phase or still active. One area that is receiving a great deal of attention is the biochemical investigation of gingival crevicular fluid (GCF). β-glucuronidase (βG) is one of the enzymes found in GCF that is involved in degradation of the ground substance and fibrillar components of host connective tissue. GCF βG activity might be a good indicator or predictor of periodontal disease activity. This study was conducted to estimate and compare the GCF βG levels in patients with healthy periodontium, chronic gingivitis, and chronic periodontitis. Subjects were classified into three groups of 20 patients each; healthy individuals, chronic gingivitis, and chronic periodontitis. After recording the plaque index, gingival index and probing pocket depth, 1 μL GCF was collected by placing a calibrated microcapillary pipette extracrevicularly and transferred to sterile plastic vials containing 350 μL of normal saline with 1% bovine serum albumin. Analysis of βG was done by spectrophotometry. βG levels in GCF were significantly higher in chronic periodontitis group (mean value - 2.04743), followed by chronic gingivitis group (mean - 1.11510) and healthy group (0.53643). Increased βG levels were observed in patients with increased periodontal destruction, hence GCF βG levels can be used as biochemical marker for periodontal disease activity.

How I manage relapse of chronic myeloid leukaemia after stopping tyrosine kinase inhibitor therapy.

PubMed

Rea, Delphine; Mahon, François-Xavier

2018-01-01

During the last 10 years, clinical trials formally demonstrated that about 50% of patients with chronic phase (CP) chronic myeloid leukaemia (CML) who achieve and maintain deep molecular responses for a prolonged period of time during treatment with imatinib or new generation tyrosine kinase inhibitors (TKIs) may successfully stop their anti-leukaemic therapy. Based on the accumulated knowledge from abundant clinical trial experience, TKI discontinuation is becoming an important goal to achieve and is about to enter clinical practice. This review focuses on relapse definition, laboratory tests to identify relapse and relapse management after TKI discontinuation. © 2017 John Wiley & Sons Ltd.

Correlation of patient entry rates and physician documentation errors in dictated and handwritten emergency treatment records.

PubMed

Dawdy, M R; Munter, D W; Gilmore, R A

1997-03-01

This study was designed to examine the relationship between patient entry rates (a measure of physician work load) and documentation errors/omissions in both handwritten and dictated emergency treatment records. The study was carried out in two phases. Phase I examined handwritten records and Phase II examined dictated and transcribed records. A total of 838 charts for three common chief complaints (chest pain, abdominal pain, asthma/chronic obstructive pulmonary disease) were retrospectively reviewed and scored for the presence or absence of 11 predetermined criteria. Patient entry rates were determined by reviewing the emergency department patient registration logs. The data were analyzed using simple correlation and linear regression analysis. A positive correlation was found between patient entry rates and documentation errors in handwritten charts. No such correlation was found in the dictated charts. We conclude that work load may negatively affect documentation accuracy when charts are handwritten. However, the use of dictation services may minimize or eliminate this effect.

Intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation: an interview study.

PubMed

Kvangarsnes, Marit; Torheim, Henny; Hole, Torstein; Öhlund, Lennart S

2013-02-01

To report a study conducted to explore intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation. An acute exacerbation is a life-threatening situation, which patients often consider to be extremely frightening. Healthcare personnel exercise considerable power in this situation, which challenges general professional notions of patient participation. Critical discourse analysis. In the autumn of 2009, three focus group interviews with experienced intensive care nurses were conducted at two hospitals in western Norway. Two groups had six participants each, and one group had five (N = 17). The transcribed interviews were analysed by means of critical discourse analysis. The intensive care nurses said that an exacerbation is often an extreme situation in which healthcare personnel are exercising a high degree of control and power over patients. Patient participation during exacerbation often takes the form of non-involvement. The participating nurses attached great importance to taking a sensitive approach when meeting patients. The nurses experienced challenging ethical dilemmas. This study shows that patient participation should not be understood in universal terms, but rather in relation to a specific setting and the interactions that occur in this setting. Healthcare personnel must develop skill, understanding, and competence to meet these challenging ethical dilemmas. A collaborative inter-professional approach between physicians and nurses is needed to meet the patients' demand for involvement. © 2012 Blackwell Publishing Ltd.

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

PubMed

Martins, Patrícia Rocha; Nascimento, Rodolfo Duarte; Lopes, Júlia Guimarães; Santos, Mônica Morais; de Oliveira, Cleida Aparecida; de Oliveira, Enio Chaves; Martinelli, Patrícia Massara; d'Ávila Reis, Débora

2015-05-01

Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

Evaluation of patients diagnosed with fascioliasis: A six-year experience at a university hospital in Turkey.

PubMed

Boşnak, Vuslat Keçik; Karaoğlan, İlkay; Sahin, Handan Haydaroğlu; Namiduru, Mustafa; Pehlivan, Mustafa; Okan, Vahap; Mete, Ayşe Özlem

2016-04-28

In this study, clinical, laboratory, radiological, and serological examinations of fascioliasis patients were analyzed, and data with a significant impact on differential diagnosis were evaluated. Clinical, radiological, and laboratory findings and treatment responses of a total of 22 fascioliasis patients, treated between October 2009 and September 2014, were evaluated. Nineteen patients were diagnosed with fascioliasis at the invasive phase and three patients at the chronic phase. Patients were followed up for clinical, laboratory, and radiology findings for a period of three months to one year after treatment. The most frequent complaints in both groups were abdominal pain, and the most common physical examination finding was epigastric tenderness. In the performed examination, an eosinophil elevation in whole blood count was detected in 19 patients (100%) in the hepatic phase, and in 2 patients (66.6%) in the biliary phase. The results of the Fasciola hepatica indirect hemagglutination assay (IHA) test ordered in the diagnosis were positive in all patients. Treatment with 10 mg/kg/day triclabendazole for two consecutive days was effective. Live parasites were extracted from patients in the biliary phase with endoscopic retrograde cholangiopancreatography. In the follow-ups, remission in IHA titer and clinical and radiological improvement was achieved in all patients. If hypereosinophilia is detected by peripheral smear in patients who are admitted with complaints such as abdominal pain, weakness, nausea, myalgia, and weight loss, radiological evaluation and serological tests should be performed and fascioliasis should be considered in the differential diagnosis.

PREDICE score as a predictor of 90 days mortality in patients with heart failure

NASA Astrophysics Data System (ADS)

Purba, D. P. S.; Hasan, R.

2018-03-01

Hospitalization in chronic heart failure patients associated with high mortality and morbidity rate. The 90 days post-discharge period following hospitalization in heart failure patients is known as the vulnerable phase, it carries the high risk of poor outcomes. Identification of high-risk individuals by using prognostic evaluation was intended to do a closer follow up and more intensive to decreasing the morbidity and mortality rate of heart failure.To determine whether PREDICE score could predict mortality within 90 days in patients with heart failure, an observational cohort study in patients with heart failure who were hospitalized due to worsening chronic heart failure. Patients were in following-up for up to 90 days after initial evaluation with the primary endpoint is death.We found a difference of the significantstatistical between PREDICE score in survival and mortality group (p=0.001) of 84% (95% CI: 60.9% - 97.4%).In conclusion, PREDICE score has a good ability to predict mortality within 90 days in patients with heart failure.

Current Management of Chronic Hepatitis B and C in Chronic Kidney Disease.

PubMed

Mikolajczyk, Adam E; Aronsohn, Andrew I

2015-09-01

The landscape of therapeutic options for hepatitis B and C has changed drastically over the course of 2 decades. There are now novel, effective, well-tolerated, oral antiviral agents being used to successfully control chronic hepatitis B (HBV) infections and cure chronic hepatitis C (HCV) infections. However, patients with CKD were rarely included in the Phase II and III randomized trials for these medications. This paucity of data and the high prevalence of comorbidities associated with CKD pose distinct challenges to physicians treating chronic hepatitis B virus and hepatitis C virus infections in the setting of kidney insufficiency/failure. Thus, this review will attempt to summarize the current data regarding novel antiviral therapies for HBV and HCV in the CKD population. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of type 2 diabetes mellitus incidence in different phases of hepatitis B virus infection: A meta-analysis.

PubMed

Shen, Yi; Zhang, Sheng; Wang, Xulin; Wang, Yuanyuan; Zhang, Jian; Qin, Gang; Li, Wenchao; Ding, Kun; Zhang, Lei; Liang, Feng

2017-10-01

Because whether hepatitis B virus infection increases the risk of type 2 diabetes mellitus has been a controversial topic, pair-wise and network meta-analyses of published literature were carried out to accurately evaluate the association between different phases of hepatitis B virus infection and the risk of type 2 diabetes mellitus. A comprehensive literature retrieval was conducted from the PubMed, Embase, Cochrane Library and Chinese Database to identify epidemiological studies on the association between hepatitis B virus infection and the risk of type 2 diabetes mellitus that were published from 1999 to 2015. A pair-wise meta-analysis of direct evidence was performed to estimate the pooled odds ratios and 95% confidence intervals. A network meta-analysis was conducted, including the construction of a network plot, inconsistency plot, predictive interval plot, comparison-adjusted funnel plot and rank diagram, to graphically link the direct and indirect comparisons between different hepatitis B virus infective phases. Eighteen publications (n=113 639) describing 32 studies were included in this meta-analysis. In the pair-wise meta-analysis, the pooled odds ratio for type 2 diabetes mellitus in chronic hepatitis B cirrhosis patients was 1.76 (95% confidence interval: 1.44-2.14) when compared with non-cirrhotic chronic hepatitis B patients. In the network meta-analysis, six comparisons of four hepatitis B virus infectious states indicated the following descending order for the risk of type 2 diabetes mellitus: hepatitis B cirrhosis patients, non-cirrhotic chronic hepatitis B patients, hepatitis B virus carriers and non-hepatitis B virus controls. This study suggests that hepatitis B virus infection is not an independent risk factor for type 2 diabetes mellitus, but the development of cirrhosis may increase the incidence of type 2 diabetes mellitus cirrhosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incidence and Time Course for Developing Heart Failure With High-Burden Right Ventricular Pacing.

PubMed

Merchant, Faisal M; Hoskins, Michael H; Musat, Dan L; Prillinger, Julie B; Roberts, Gregory J; Nabutovsky, Yelena; Mittal, Suneet

2017-06-01

Although right ventricular pacing can contribute to cardiomyopathy, the impact of complete atrioventricular block (cAVB) on heart failure (HF) development in pacemaker patients has not been well characterized. We evaluated the incidence and time course for developing HF after pacemaker implantation for cAVB. A MarketScan database identified patients undergoing dual-chamber pacemaker implantation from 2008 to 2014. Patients with cAVB were identified by an atrioventricular node ablation or diagnosis of third-degree AVB. Patients with ≥1 year of continuous MarketScan enrollment before and after implant and without a previous diagnosis of HF were dichotomized into those with cAVB and without AVB. The primary end point was new HF assessed over acute (0-6 months) and chronic (6 months to 4 years) phases post-pacemaker implantation. The cohort included 6994 cAVB patients and 14 208 patients without AVB, followed for 2.35 years (interquartile range, 1.62-3.39 years). After adjustment for baseline covariates, patients with cAVB experienced an increased risk of new-onset HF in the acute phase (hazard ratio, 1.62; 95% confidence interval, 1.48-1.79; P <0.001). Although the risk of HF remained elevated among those with cAVB in the chronic phase, the effect was attenuated (hazard ratio, 1.16; 95% confidence interval, 1.08-1.25; P <0.001). After pacemaker implantation, younger patients (≤55 years of age) and those with an antecedent history of atrial fibrillation experienced the highest risk of HF associated with cAVB. Patients with a diagnosis of cAVB, and thus presumed to have a higher burden of right ventricular pacing, experienced an increased risk of new-onset HF after pacemaker implantation compared with those without AVB. Better tools are needed to identify patients at high risk of developing HF in the setting of right ventricular pacing and to determine whether these patients benefit from upfront biventricular pacing. © 2017 American Heart Association, Inc.

Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowan-Jacob, Sandra W., E-mail: sandra.jacob@novartis.com; Fendrich, Gabriele; Floersheimer, Andreas

2007-01-01

A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 suchmore » point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.« less

Psychometric validation of the Psoriasis Symptom Diary using Phase III study data from patients with chronic plaque psoriasis.

PubMed

Strober, Bruce; Zhao, Yang; Tran, Mary Helen; Gnanasakthy, Ari; Nyirady, Judit; Papavassilis, Charis; Nelson, Lauren M; McLeod, Lori D; Mordin, Margaret; Gottlieb, Alice B; Elewski, Boni E; Lebwohl, Mark

2016-03-01

This analysis aimed to confirm the reliability, validity, and responsiveness of the Psoriasis Symptom Diary (PSD) using data from two Phase III studies in patients with moderate to severe chronic plaque psoriasis. Data from two randomized, double-blind, double-dummy, placebo-controlled, multicenter Phase III studies (n = 820) assessing the efficacy and safety of secukinumab were used. The PSD (24-h recall; 0-10 numeric rating scale) was electronically administered each evening. Test-retest reliability was determined using intraclass correlations. Construct validity hypotheses were evaluated via correlations with the Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI), EuroQoL 5-Dimension Health Status Questionnaire, and Patient Global Impression of Change (PGIC). Discriminating ability and responsiveness were evaluated by estimating mean differences and effect sizes between known groups (using the PASI and IGA). Phase II-derived, anchor-based PGIC thresholds and cumulative distribution function (CDF) plots described meaningful change. Items on the PSD yielded high intraclass coefficients (>0.90). Correlations were in the anticipated direction and by week 12 were moderate to strong (0.41-0.73) in magnitude, demonstrating construct validity. Average PSD item scores differed predictably and significantly between known groups. Responsiveness effect size estimates were moderate to large (0.6-1.5), and CDF plots showed the percentage of responders to be consistently higher in treatment than in placebo arms across the range of change in PSD scores. The PSD is reliable, valid, and responsive, and represents a valid tool to enhance treatment decisions in patients with moderate to severe plaque psoriasis. © 2015 The International Society of Dermatology.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

PubMed

Marzel, Alex; Shilaih, Mohaned; Yang, Wan-Lin; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Braun, Dominique L; Calmy, Alexandra; Furrer, Hansjakob; Cavassini, Matthias; Battegay, Manuel; Vernazza, Pietro L; Bernasconi, Enos; Günthard, Huldrych F; Kouyos, Roger D; Aubert, V; Battegay, M; Bernasconi, E; Böni, J; Bucher, H C; Burton-Jeangros, C; Calmy, A; Cavassini, M; Dollenmaier, G; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, C A; Gorgievski, M; Günthard, H F; Haerry, D; Hasse, B; Hirsch, H H; Hoffmann, M; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kouyos, R D; Kovari, H; Ledergerber, B; Martinetti, G; de Tejada, B Martinez; Metzner, K; Müller, N; Nadal, D; Nicca, D; Pantaleo, G; Rauch, A; Regenass, S; Rickenbach, M; Rudin, C; Schöni-Affolter, F; Schmid, P; Schüpbach, J; Speck, R; Tarr, P; Trkola, A; Vernazza, P L; Weber, R; Yerly, S

2016-01-01

Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Management of chronic ankle pain using joint mobilization and ASTYM® treatment: a case report.

PubMed

Slaven, Emily J; Mathers, Jessie

2011-05-01

Treatment of ankle sprains predominately focuses on the acute management of this condition; less emphasis is placed on the treatment of ankle sprains in the chronic phase of recovery. Manual therapy, in the form of joint mobilization and manipulation, has been shown to be effective in the management of this condition, but the combination of joint mobilization and manipulation in tandem with ASTYM® treatment has not been explored. The purpose of this case report is to chronicle the management of a patient with chronic ankle pain who was treated with manual therapy including manipulation and ASTYM treatment. As a result of a fall down stairs 6 months previously, the patient sustained a severe ankle sprain. The soft tissue damage was accompanied by bony disruptions which warranted the patient spending 3 weeks in a walking boot. At the initial evaluation, the patient reported difficulty with descending stairs reciprocally and not being able to run more than 4 minutes on the treadmill before the pain escalated to the level that she had to stop running. After five sessions of therapy consisting of joint mobilization, manipulation and ASTYM, the patient was able to descend stairs and run 40 minutes without pain.

Bacterial Contribution in Chronicity of Wounds.

PubMed

Rahim, Kashif; Saleha, Shamim; Zhu, Xudong; Huo, Liang; Basit, Abdul; Franco, Octavio Luiz

2017-04-01

A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.

Targeting inflammation: new therapeutic approaches in chronic kidney disease (CKD).

PubMed

Impellizzeri, Daniela; Esposito, Emanuela; Attley, James; Cuzzocrea, Salvatore

2014-03-01

Chronic inflammation and oxidative stress, features that are closely associated with nuclear factor (NF-κB) activation, play a key role in the development and progression of chronic kidney disease (CKD). Several animal models and clinical trials have clearly demonstrated the effectiveness of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy to improve glomerular/tubulointerstitial damage, reduce proteinuria, and decrease CKD progression, but CKD treatment still represents a clinical challenge. Bardoxolone methyl, a first-in-class oral Nrf-2 (nuclear factor erythroid 2-related factor 2) agonist that until recently showed considerable potential for the management of a range of chronic diseases, had been shown to improve kidney function in patients with advanced diabetic nephropathy (DN) with few adverse events in a phase 2 trial, but a large phase 3 study in patients with diabetes and CKD was halted due to emerging toxicity and death in a number of patients. Instead, palmitoylethanolamide (PEA) a member of the fatty acid ethanolamine family, is a novel non-steroidal, kidney friendly anti-inflammatory and anti-fibrotic agent with a well-documented safety profile, that may represent a potential candidate in treating CKD probably by a combination of pharmacological properties, including some activity at the peroxisome proliferator activated receptor alpha (PPAR-α). The aim of this review is to discuss new therapeutic approaches for the treatment of CKD, with particular reference to the outcome of two therapies, bardoxolone methyl and PEA, to improve our understanding of which pharmacological properties are responsible for the anti-inflammatory effects necessary for the effective treatment of renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel Oral Therapies for Opioid-induced Bowel Dysfunction in Patients with Chronic Noncancer Pain.

PubMed

Holder, Renee M; Rhee, Diane

2016-03-01

Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are needed to further define their role in therapy. © 2016 Pharmacotherapy Publications, Inc.

Modeling and Simulation of Pivotal Clinical Trials Using Linked Models for Multiple Endpoints in Chronic Obstructive Pulmonary Disease With Roflumilast.

PubMed

Facius, Axel; Krause, Andreas; Claret, Laurent; Bruno, Rene; Lahu, Gezim

2017-08-01

Roflumilast is a selective phosphodiesterase 4 inhibitor (PDE4i) for the treatment of severe chronic obstructive pulmonary disease (COPD). In 2 large phase 3 trials in a broader population of COPD patients (BY217/M2-111, ClinicalTrials.gov: NCT00076089 and BY217/M2-112, ClinicalTrials.gov: NCT00430729), treatment with roflumilast reduced the rate of exacerbations; however, the reduction did not reach statistical significance. Two linked dose-response models for the primary (annualized COPD exacerbation counts) and secondary (change from baseline in forced expiratory volume in 1 second [FEV 1 ]) end points were therefore developed to characterize and quantify effect sizes and the patient characteristics influencing them. The models showed that disease severity and bronchitis, particularly the severity of bronchitis expressed in cough-and-sputum scores, were good predictors of exacerbation rates and differential benefit of roflumilast in exacerbation reduction. The models were used to support the rational design of 2 phase 3 randomized, placebo-controlled clinical trials (BY217/M2-124, ClinicalTrials.gov: NCT00297102 and BY217/M2-125, ClinicalTrials.gov: NCT00297115) by identifying the most appropriate patient population using clinical trial simulations. Model predictions for both end points were found to be highly accurate - as confirmed by the results from these trials, which led to the approval of roflumilast as the first oral PDE4i for the treatment of COPD in patients associated with chronic bronchitis and a history of exacerbations. © 2017, The American College of Clinical Pharmacology.

Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.

PubMed

Ikonomidis, Ignatios; Athanassopoulos, George; Stamatelopoulos, Kimon; Lekakis, John; Revela, Ioanna; Venetsanou, Kiriaki; Marinou, Margarita; Monaco, Claudia; Cokkinos, Dennis V; Nihoyannopoulos, Petros

2008-08-01

Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD). We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated. Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P < .01 for an adverse event). The addition of peak wall motion score index in a multivariable model including risk factors, ejection fraction, revascularization, and multivessel disease increased the model's c statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events. Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD.

Lubiprostone increases spontaneous bowel movement frequency and quality of life in patients with chronic idiopathic constipation.

PubMed

Fukudo, Shin; Hongo, Michio; Kaneko, Hiroshi; Takano, Masahiro; Ueno, Ryuji

2015-02-01

Lubiprostone is an activator of the type 2 chloride channel that facilitates spontaneous bowel movement (SBM). We performed phase 3 studies to determine whether lubiprostone increases the frequency of SBM in patients with chronic idiopathic constipation (CIC) in Japan, and whether long-term administration of lubiprostone increases the quality of life of patients with CIC. We performed a randomized, double-blind, placebo-controlled, phase 3 trial of lubiprostone. Patients with CIC (n = 124) were assigned randomly to groups given placebo (n = 62) or lubiprostone (48 μg/day; n = 62) for 4 weeks. The primary efficacy end point was the change from baseline in the weekly average number of SBMs after 1 week of administration. In a long-term study of efficacy and safety, 209 patients with CIC were given lubiprostone (24 μg twice daily) for 48 weeks. Daily administration of lubiprostone induced a significantly greater change, from baseline, in the weekly average number of SBMs at week 1 (increase of 3.7 ± 2.8), compared with placebo (increase of 1.3 ± 1.8; P < .001). The frequency of SBMs during each week of the study period was significantly higher after subjects began receiving lubiprostone than at baseline (P < .0001 at all weeks). Long-term administration of lubiprostone significantly increased scores from the Short-Form health survey and irritable bowel syndrome quality-of-life questionnaire, compared with baseline. We did not observe any severe adverse reactions to lubiprostone. In phase 3 studies in Japan, lubiprostone increased the weekly average number of SBMs and increased the quality of life of patients with CIC. Clinical Trial Notification of the Japanese Regulatory Authorities: 20-3296 and 20-3300. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Health Care Costs for Patients With Chronic Spinal Cord Injury in the Veterans Health Administration

PubMed Central

French, Dustin D; Campbell, Robert R; Sabharwal, Sunil; Nelson, Audrey L; Palacios, Polly A; Gavin-Dreschnack, Deborah

2007-01-01

Background/Objective: Recurring annual costs of caring for patients with chronic spinal cord injury (SCI) is a large economic burden on health care systems, but information on costs of SCI care beyond the acute and initial postacute phase is sparse. The objective of this study was to establish a frame of reference and estimate of the annual direct medical costs associated with health care for a sample of patients with chronic SCI (ie, >2 years after injury). Methods: Patients were recruited from 3 Veterans Health Administration (VHA) SCI facilities; baseline patient information was cross-referenced to the Decision Support System (DSS) National Data Extracts (NDE) to obtain patient-specific health care costs in VHA. Descriptive statistical analysis of annual DSS-NDE cost of patients with SCI (N = 675) for fiscal year (FY) 2005 by level and completeness of injury was conducted. Results: Total (inpatient and outpatient) annual (FY 2005) direct medical costs for 675 patients with SCI exceeded $14.47 million or $21,450 per patient. Average annual total costs varied from $28,334 for cervical complete SCI to $16,792 for thoracic incomplete SCI. Two hundred thirty-three of the 675 patients with SCI who were hospitalized over the study period accounted for a total of 378 hospital discharges, costing in excess of $7.19 million. This approximated a cost of outpatient care received of $7.28 million for our entire sample. Conclusions: The comprehensive nature of health care delivery and related cost capture for people with chronic SCI in the VHA provided us the opportunity to accurately determine health care costs for this population. Future SCI postacute care cost analyses should consider case-mix adjusting patients at high risk for rehospitalization. PMID:18092564

Task-oriented treadmill exercise training in chronic hemiparetic stroke

PubMed Central

Ivey, Frederick M.; Hafer-Macko, Charlene E.; Macko, Richard F.

2010-01-01

Patients with stroke have elevated hemiparetic gait costs secondary to low activity levels and are often severely deconditioned. Decrements in peak aerobic capacity affect functional ability and cardiovascular-metabolic health and may be partially mediated by molecular changes in hemiparetic skeletal muscle. Conventional rehabilitation is time delimited in the subacute stroke phase and does not provide adequate aerobic intensity to reverse the profound detriments to fitness and function that result from stroke. Hence, we have studied progressive full body weight-support treadmill (TM) training as an adjunct therapy in the chronic stroke phase. Task-oriented TM training has produced measurable changes in fitness, function, and indices of cardiovascular-metabolic health after stroke, but the precise mechanisms for these changes remain under investigation. Further, the optimal dose of this therapy has yet to be identified for individuals with stroke and may vary as a function of deficit severity and outcome goals. This article summarizes the functional and metabolic decline caused by inactivity after stroke and provides current evidence that supports the use of TM training during the chronic stroke phase, with protocols and inclusion/exclusion criteria described. Our research findings are discussed in relation to associated research. PMID:18566943

[Clinical experiences with four newly developed, surface modified stimulation electrodes].

PubMed

Winter, U J; Fritsch, J; Liebing, J; Höpp, H W; Hilger, H H

1993-05-01

Newly developed pacing electrodes with so-called porous surfaces promise a significantly improved post-operative pacing and sensing threshold. We therefore investigated four newly developed leads (ELA-PMCF-860 n = 10; Biotronik-60/4-DNP n = 10, CPI-4010 n = 10, Intermedics-421-03-Biopore n = 6) connected to two different pacing devices (Intermedics NOVA II, Medtronic PASYS) in 36 patients (18 men, 18 women, age: 69.7 +/- 9.8 years) suffering from symptomatic bradycardia. The individual electrode maturation process was investigated by means of repeated measurements of pacing threshold, electrode impedance in acute, subacute, and chronic phase, as well as energy consumption and sensing behavior in the chronic phase. However, with the exception of the 4010, the investigated leads showed largely varying values of the pacing threshold with individual peaks occurring from the second up to the 13th week. All leads had nearly similar chronic pacing thresholds (PMCF 0.13 +/- 0.07; DNP 0.25 +/- 0.18; Biopore 0.15 +/- 0.05; 4010 0.14 +/- 0.05 ms). Impedance measurements revealed higher, but not significantly different values for the DNP (PMCF 582 +/- 112, DNP 755 +/- 88, Biopore 650 +/- 15, 4010 718 +/- 104 Ohm). Despite differing values for pacing threshold and impedance, the energy consumption in the chronic phase during threshold-adapted, but secure stimulation (3 * impulse-width at pacing threshold) were comparable.

Impact of Obesity and Other Chronic Conditions on Lifestyle Exercise During the Year After Completion of Cardiac Rehabilitation.

PubMed

Sattar, Abdus; Josephson, Richard; Moore, Shirley M

2017-07-01

Patients who attend cardiac rehabilitation programs have a high prevalence of multiple chronic conditions (MCCs). The extent to which different constellations of MCC influence lifestyle exercise in the year after completion of an outpatient phase 2 cardiac rehabilitation program (CRP) is unknown. Our objective was to examine the effects of MCC on lifestyle exercise in the year after completion of a CRP. The effects of different constellations of comorbidities on objectively measured lifestyle exercise were examined using data from a randomized controlled trial testing lifestyle behavior change interventions in patients with cardiac events (n = 379) who completed a phase 2 CRP. Adjusting for important covariates, the relationships between the primary outcome, exercise amount, and the presence of common chronic conditions (hypertension, obesity, diabetes, and arthritis) were studied using robust linear mixed-effects models. Diabetes, hypertension, obesity, and their dyads, triads, and quads have a negative impact on amount of exercise. For example, the cooccurrences of obesity and hypertension reduced lifestyle exercise by 2.83 hours per month (95% CI, 1.33-4.33) after adjustment for the effects of covariates. The presence of obesity was a major factor in the comorbid constellations affecting lifestyle exercise. The presence of obesity and other chronic conditions negatively impacts lifestyle exercise in the year after a CRP. The magnitude of the effect depends on the comorbidities. Different constellations of comorbid conditions can be used to identify those persons at greatest risk for not exercising after cardiac rehabilitation.

Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

PubMed

Onida, Francesco; de Wreede, Liesbeth C; van Biezen, Anja; Eikema, Diderik-Jan; Byrne, Jenny L; Iori, Anna P; Schots, Rik; Jungova, Alexandra; Schetelig, Johannes; Finke, Jürgen; Veelken, Hendrik; Johansson, Jan-Erik; Craddock, Charles; Stelljes, Matthias; Theobald, Matthias; Holler, Ernst; Schanz, Urs; Schaap, Nicolaas; Bittenbring, Jörg; Olavarria, Eduardo; Chalandon, Yves; Kröger, Nicolaus

2017-06-01

Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates. © 2017 John Wiley & Sons Ltd.

Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings.

PubMed

Patel, Hitesh C; Hayward, Carl; Dungu, Jason N; Papadopoulou, Sofia; Saidmeerasah, Abdel; Ray, Robin; Di Mario, Carlo; Shanmugam, Nesan; Cowie, Martin R; Anderson, Lisa J

2017-07-01

To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Planned Pregnancy in a Chronic Myeloid Leukemia Patient in Molecular Remission

PubMed Central

Pavlovsky, Carolina; Giere, Isabel; Van Thillo, Germán

2012-01-01

Excellent response rates and a good quality of life have been observed since the introduction of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) treatment. Consequently, some challenges began to appear in CML women in child-bearing age wishing to become pregnant. Currently, many women around the world are in stable major/complete molecular response MMR/CMR (MMR: <0.1% BCR-ABL/ABL and CMR: undetectable BCR-ABL mRNA by RQ-PCR transcript levels on the international scale). The condition of stable MMR/CMR is linked to a long-term virtual absence of progression to the accelerated and blastic phase and to the possibility of stopping the TKI treatment with the maintenance of a condition of CMR in a proportion of cases. Imatinib teratogenic and prescribing information prohibits the use of it during pregnancy. We describe the case of a 36-year-old female patient with CML in chronic phase who stopped imatinib after 2 years in major molecular response (MMR) to plan a pregnancy. Molecular monitoring by RQ-PCR was performed quarterly. She achieved a safe pregnancy and delivery maintaining an optimal molecular response throughout the pregnancy. Isolated literature reports have been described, but no formal advice has been described at present time. PMID:22928126

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

PubMed

Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine; Christensen, Anne Marie Raaberg; Nordentoft, Merete; Mortensen, Erik Lykke

2013-10-01

Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms. © 2013 The Scandinavian Psychological Associations.

A multidisciplinary network for the care of abnormal fatigue and chronic fatigue syndrome in the provinces of East and West Flanders in Belgium.

PubMed

Tobback, E; Mariman, A; Heytens, S; Declercq, T; Bouwen, A; Spooren, D; Snoeck, P; Van Dessel, K; D'Hooghe, S; Rimbaut, S; Vogelaers, D

2014-10-01

The organization of care for patients with the chronic fatigue syndrome (CFS) in tertiary care referral centres from 2002 onwards, was negatively evaluated by the Belgian Health Care Knowledge Centre on the endpoint of socio-professional reintegration. Subsequently, the federal health authorities asked for the elaboration of a new and innovative model of stepped care, aiming at improved integration of diagnosis and treatment into primary care and between levels of health care for patients with CFS. The reference centre of the University Hospital Ghent took the initiative of recruiting partners in the Belgian provinces of East and West Flanders to guarantee the care for patients with medically unexplained symptoms, in particular abnormal fatigue and CFS. A new and innovative care model, in which general practitioners play a central role, emphasizes the importance of early recognition of the patient 'at risk', correct diagnosis and timely referral. Early detection and intervention is essential in order to avoid or minimize illness progression towards chronicity, to safeguard opportunities for significant health improvement as well as to enhance successful socio-professional reintegration. This approach covers both the large sample of patients developing somatic complaints without obvious disease in an early phase as well as the more limited group of patients with chronic illness, including CFS. Cognitive behavioural therapy and graded exposure/exercise therapy are the evidence based main components of therapy in the latter. A biopsychosocial model underlies the proposed path of care.

Chronic atherosclerotic mesenteric ischemia that started to develop symptoms just after anaphylaxis.

PubMed

Goto, M; Matsuzaki, M; Fuchinoue, A; Urabe, N; Kawagoe, N; Takemoto, I; Tanaka, H; Watanabe, T; Miyazaki, T; Takeuchi, M; Honda, Y; Nakanishi, K; Urita, Y; Shimada, N; Nakajima, H; Sugimoto, M; Goto, T

2012-05-01

An 83-year-old woman was referred to our emergency department with acute urticaria and sudden shortness of breath approximately 30 min after taking rectal diclofenac potassium for lumbago. After treatment with adrenaline and corticosteroids, the patient became hemodynamically stable and left the hospital on the next day. She attended our hospital 1 week after the onset of anaphylaxis because of repeated postprandial epigastric pain. No abnormal lesions were found in endoscopy. Radiographic selective catheter angiography revealed chronic mesenteric ischemia caused by atherosclerosis and abundant collateral arteries between the celiac trunk, the superior mesenteric artery and the inferior mesenteric artery. Patients with chronic mesenteric ischemia usually present with a clinical syndrome characterized by painful abdominal cramps and colic occurring typically during the postprandial phase. Fear of eating resulted in malnutrition. She was prescribed proton pump inhibitor, digestants, anticholinergic agents, serine protease inhibitors, prokinetics, antiplatelet agents and transdermal nitroglycerin intermittently, but these had no beneficial effects. It was most probable that this patient with chronic atherosclerotic mesenteric ischemia was suffering from functional abdominal pain syndrome induced by anaphylaxis. Since psychiatric disorders were associated with alterations in the processing of visceral sensation, we facilitated the patient's understanding of functional abdominal pain syndrome with the psychologist. Postprandial abdominal pain gradually faded after administration of these drugs and the patient left the hospital. Developing a satisfactory patient-physician relationship was considered more effective for the management of persistent abdominal pain caused by complicated mechanisms.

Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors.

PubMed

Pitt, Bertram; Bakris, George L; Bushinsky, David A; Garza, Dahlia; Mayo, Martha R; Stasiv, Yuri; Christ-Schmidt, Heidi; Berman, Lance; Weir, Matthew R

2015-10-01

We evaluated the effects of patiromer, a potassium (K(+))-binding polymer, in a pre-specified analysis of hyperkalaemic patients with heart failure (HF) in the OPAL-HK trial. Chronic kidney disease (CKD) patients on renin-angiotensin-aldosterone system inhibitors (RAASi) with serum K(+) levels ≥5.1 mEq/L to <6.5 mEq/L (n = 243) received patiromer (4.2 g or 8.4 g BID initially) for 4 weeks (initial treatment phase); the primary efficacy endpoint was mean change in serum K(+) from baseline to week 4. Eligible patients (those with baseline K(+) ≥5.5 mEq/L to <6.5 mEq/L and levels ≥3.8 mEq/L to <5.1 mEq/L at the end of week 4) entered an 8-week randomized withdrawal phase and were randomly assigned to continue patiromer or switch to placebo; the primary efficacy endpoint was the between-group difference in median change in the serum K(+) over the first 4 weeks of that phase. One hundred and two patients (42%) had heart failure (HF). The mean [± standard error (SE)] change in serum K(+) from baseline to week 4 was -1.06 ± 0.05 mEq/L [95% confidence interval (CI), -1.16,-0.95; P < 0.001]; 76% (95% CI, 69,84) achieved serum K(+), 3.8 mEq/L to <5.1 mEq/L. In the randomized withdrawal phase, the median increase in serum K(+) from baseline of that phase was greater with placebo (n = 22) than patiromer (n = 27) (P < 0.001); recurrent hyperkalaemia (serum K(+), ≥5.5 mEq/L) occurred in 52% on placebo and 8% on patiromer (P < 0.001). Mild-to-moderate constipation was the most common adverse event (11%); hypokalaemia occurred in 3%. In patients with CKD and HF who were hyperkalaemic on RAASi, patiromer was well tolerated, decreased serum K(+), and, compared with placebo, reduced recurrent hyperkalaemia. © 2015 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Population pharmacokinetic modeling of epoetin delta in pediatric patients with chronic kidney disease.

PubMed

Knebel, William; Palmen, Mary; Dowell, James A; Gastonguay, Marc

2008-07-01

This analysis quantifies the population pharmacokinetics of subcutaneous and intravenous epoetin delta, an epoetin produced in a human cell line, in pediatric patients with chronic kidney disease and estimates the effects of covariate factors on epoetin delta and epoetin alfa pharmacokinetic parameters. Erythropoietin serum concentration data, taken from a phase III study conducted in 60 patients aged 1 to 17 years, were best described by a 1-compartment model with first-order absorption and elimination. The typical point estimates were clearance (0.268 L/h), central volume of distribution (1.03 L), absorption rate constant (0.0554 h(-1)), and bioavailability (0.708) for a 35-kg male < or = 10 years who was predialysis and on subcutaneous epoetin delta treatment. Erythropoietin pharmacokinetic parameters were similar in pediatric patients as compared with adults when scaled by weight. The subcutaneous administration of epoetin alfa exhibited lower systemic bioavailability than subcutaneous administration of epoetin delta.

Exploring eHealth Ethics and Multi-Morbidity: Protocol for an Interview and Focus Group Study of Patient and Health Care Provider Views and Experiences of Using Digital Media for Health Purposes.

PubMed

Townsend, Anne; Adam, Paul; Li, Linda C; McDonald, Michael; Backman, Catherine L

2013-10-17

eHealth is a broad term referring to the application of information and communication technologies in the health sector, ranging from health records to medical consultations (telemedicine) and multiple forms of health education, support, and tools. By providing increased and anytime access to information, opportunities to exchange experiences with others, and self-management support, eHealth has been heralded as transformational. It has the potential to accelerate the shift from traditional "passive patient" to an informed, engaged, and empowered "patient as partner," equipped to take part in shared decision-making, and take personal responsibility for self-managing their illness. The objective of our study is to examine how people with chronic illness use eHealth in their daily lives, how it affects patient-provider relationships, and the ethical and practical ramifications for patients, providers, and service delivery. This two-phase qualitative study is ongoing. We will purposively sample 60-70 participants in British Columbia, Canada. To be eligible, patient participants have to have arthritis and at least one other chronic health condition; health care providers (HCPs) need a caseload of patients with multi-morbidity (>25%). To date we have recruited 36 participants (18 patients, 18 HCPs). The participants attended 7 focus groups (FGs), 4 with patients and 3 with rehabilitation professionals and physicians. We interviewed 4 HCPs who were unable to attend a FG. In phase 2, we will build on FG findings and conduct 20-24 interviews with equal numbers of patients and HCPs (rehabilitation professionals and physicians). As in the FGs conducted in phase I, the interviews will use a semistructured, but flexible, discussion guide. All discussions are being audiotaped and transcribed verbatim. Constant comparisons and a narrative approach guides the analyses. A relational ethics conceptual lens is being applied to the data to identify emergent ethical issues. This study explores ethical issues in eHealth. Our goal is to identify the role of eHealth in the lives of people with multiple chronic health conditions and to explore how eHealth impacts the patient role, self-managing, and the patient-HCP relationship. The ethical lens facilitates a systematic critical analysis of emergent ethical issues for further investigation and pinpoints areas of practice that require interventions as eHealth develops and use increases both within and outside of the clinical setting. The potential benefits and burdens of eHealth need to be identified before an ethical framework can be devised.

Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

PubMed

Kung, P C; Long, J C; McCaffrey, R P; Ratliff, R L; Harrison, T A; Baltimore, D

1978-05-01

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

PubMed Central

Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

2015-01-01

Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune encephalomyelitis (EAE) represents a reliable model of the chronic-progressive variant of MS. fMRI studies in EAE have not been performed extensively up to now. This paper reports fMRI studies in a rat model of MS with somatosensory stimulation of the forepaw. We demonstrated modifications in the recruitment of cortical areas consistent with data from MS patients. To the best of our knowledge, this is the first report of cortical remodeling in a preclinical in vivo model of MS. PMID:26157006

Measuring organizational readiness for knowledge translation in chronic care.

PubMed

Gagnon, Marie-Pierre; Labarthe, Jenni; Légaré, France; Ouimet, Mathieu; Estabrooks, Carole A; Roch, Geneviève; Ghandour, El Kebir; Grimshaw, Jeremy

2011-07-13

Knowledge translation (KT) is an imperative in order to implement research-based and contextualized practices that can answer the numerous challenges of complex health problems. The Chronic Care Model (CCM) provides a conceptual framework to guide the implementation process in chronic care. Yet, organizations aiming to improve chronic care require an adequate level of organizational readiness (OR) for KT. Available instruments on organizational readiness for change (ORC) have shown limited validity, and are not tailored or adapted to specific phases of the knowledge-to-action (KTA) process. We aim to develop an evidence-based, comprehensive, and valid instrument to measure OR for KT in healthcare. The OR for KT instrument will be based on core concepts retrieved from existing literature and validated by a Delphi study. We will specifically test the instrument in chronic care that is of an increasing importance for the health system. Phase one: We will conduct a systematic review of the theories and instruments assessing ORC in healthcare. The retained theoretical information will be synthesized in a conceptual map. A bibliography and database of ORC instruments will be prepared after appraisal of their psychometric properties according to the standards for educational and psychological testing. An online Delphi study will be carried out among decision makers and knowledge users across Canada to assess the importance of these concepts and measures at different steps in the KTA process in chronic care.Phase two: A final OR for KT instrument will be developed and validated both in French and in English and tested in chronic disease management to measure OR for KT regarding the adoption of comprehensive, patient-centered, and system-based CCMs. This study provides a comprehensive synthesis of current knowledge on explanatory models and instruments assessing OR for KT. Moreover, this project aims to create more consensus on the theoretical underpinnings and the instrumentation of OR for KT in chronic care. The final product--a comprehensive and valid OR for KT instrument--will provide the chronic care settings with an instrument to assess their readiness to implement evidence-based chronic care.

Measuring organizational readiness for knowledge translation in chronic care

PubMed Central

2011-01-01

Background Knowledge translation (KT) is an imperative in order to implement research-based and contextualized practices that can answer the numerous challenges of complex health problems. The Chronic Care Model (CCM) provides a conceptual framework to guide the implementation process in chronic care. Yet, organizations aiming to improve chronic care require an adequate level of organizational readiness (OR) for KT. Available instruments on organizational readiness for change (ORC) have shown limited validity, and are not tailored or adapted to specific phases of the knowledge-to-action (KTA) process. We aim to develop an evidence-based, comprehensive, and valid instrument to measure OR for KT in healthcare. The OR for KT instrument will be based on core concepts retrieved from existing literature and validated by a Delphi study. We will specifically test the instrument in chronic care that is of an increasing importance for the health system. Methods Phase one: We will conduct a systematic review of the theories and instruments assessing ORC in healthcare. The retained theoretical information will be synthesized in a conceptual map. A bibliography and database of ORC instruments will be prepared after appraisal of their psychometric properties according to the standards for educational and psychological testing. An online Delphi study will be carried out among decision makers and knowledge users across Canada to assess the importance of these concepts and measures at different steps in the KTA process in chronic care. Phase two: A final OR for KT instrument will be developed and validated both in French and in English and tested in chronic disease management to measure OR for KT regarding the adoption of comprehensive, patient-centered, and system-based CCMs. Discussion This study provides a comprehensive synthesis of current knowledge on explanatory models and instruments assessing OR for KT. Moreover, this project aims to create more consensus on the theoretical underpinnings and the instrumentation of OR for KT in chronic care. The final product--a comprehensive and valid OR for KT instrument--will provide the chronic care settings with an instrument to assess their readiness to implement evidence-based chronic care. PMID:21752264

[Risk factors associated with the diagnosis of chronic Chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela].

PubMed

González, Beatriz; Silva, Martha; Al-Atrache, Yusra; Delgado, Yelitze; Serrano, José Luis; Doccimo, Angelina; Hernández, Huber; Verde, Juan; Morillo, Daniela; Marín, Jaime; Concepción, Juan Luis; Bonfante-Cabarcas, Rafael; Rodríguez-Bonfante, Claudina

2014-06-01

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual. Risk factors were determined through binary logistic regression. Results showed that 81 patients (70,4%; CI 95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC 95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC 95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC 95% = 4.0-8.2) in phase III. In a one year period, two patients in phase III died of heart failure. The diagnosis of CChM was associated with hunting practice, maternal history of cardiopathies, chewing chimó, medical history of hypertension and apex beat visible; it was negatively associated with canned and preserved foods ingest. In conclusion the CChM diagnosis has high frequency in seropositive individuals in Barinas and heart failure prevention must be based on an early medical attention and educative strategies in order to control risk factors.

Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists.

PubMed

Prost, Stéphane; Relouzat, Francis; Spentchian, Marc; Ouzegdouh, Yasmine; Saliba, Joseph; Massonnet, Gérald; Beressi, Jean-Paul; Verhoeyen, Els; Raggueneau, Victoria; Maneglier, Benjamin; Castaigne, Sylvie; Chomienne, Christine; Chrétien, Stany; Rousselot, Philippe; Leboulch, Philippe

2015-09-17

Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this hypothesis. CML is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR-ABL. During the chronic phase, this sole genetic abnormality (chromosomal translocation Ph(+): t(9;22)(q34;q11)) at the stem cell level causes increased proliferation of myeloid cells without loss of their capacity to differentiate. Without treatment, most patients progress to the blast phase when additional oncogenic mutations result in a fatal acute leukaemia made of proliferating immature cells. Imatinib mesylate and other tyrosine kinase inhibitors (TKIs) that target the kinase activity of BCR-ABL have improved patient survival markedly. However, fewer than 10% of patients reach the stage of complete molecular response (CMR), defined as the point when BCR-ABL transcripts become undetectable in blood cells. Failure to reach CMR results from the inability of TKIs to eradicate quiescent CML leukaemia stem cells (LSCs). Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α and CITED2, which are key guardians of the quiescence and stemness of CML LSCs. When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool.

Long-term follow up of peginterferon-α-2a treatment of hepatitis B e-antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies.

PubMed

Okanoue, Takeshi; Shima, Toshihide; Hasebe, Chitomi; Karino, Yoshiyasu; Imazeki, Fumio; Kumada, Takashi; Minami, Masahito; Imai, Yasuharu; Yoshihara, Harumasa; Mita, Eiji; Morikawa, Teruhisa; Nishiguchi, Shuhei; Kawakami, Yoshiiku; Nomura, Hideyuki; Sakisaka, Shotaro; Kurosaki, Masayuki; Yatsuhashi, Hiroshi; Oketani, Makoto; Kohno, Hiroshi; Masumoto, Akihide; Ikeda, Kenji; Kumada, Hiromitsu

2016-09-01

We analyzed the 5-year post-treatment response to peginterferon α-2a (PEG IFN-α-2a) in hepatitis B e-antigen (HBeAg) positive and negative chronic hepatitis B patients. One hundred and thirty-seven chronic hepatitis B (CHB) patients receiving 90 μg or 180 μg of PEG IFN-α-2a for 24 or 48 weeks in phase II or III studies were enrolled in the study, including 100 HBeAg positive patients and 37 HBeAg negative patients; 121 patients (88.4%) had genotype C. Of the 137 patients, 94 received additional antiviral therapy because of viral reactivation and 43 did not receive any additional antiviral treatment during follow up. Five years upon PEG IFN-α-2a treatment, 32 patients (23.4%) who did not receive any additional antiviral agent after PEG IFN-α-2a therapy achieved a good response (normal serum alanine aminotransferase, low-level hepatitis B virus [HBV] DNA, and HBeAg negativity). Female sex and low HBV DNA levels by the end of treatment were independently associated with favorable 5-year post-treatment responses. Forty-eight-week administration of PEG IFN-α-2a showed a better response (26.4%) than 24-week administration (18.0%). Six patients (4.3%), four males and two females, cleared hepatitis B surface antigen (HBsAg) during the 5-year follow-up period. The 48-week administration of PEG IFN-α-2a achieved better biochemical and virological responses than the 24-week administration, particularly in younger females. The 5-year post-treatment response rate was 23.4%; however, more than two-thirds of the patients received additional antiviral therapy because of viral reactivation after PEG IFN-α-2a treatment. HBsAg clearance was noted in six patients (4.3%). PEG IFN-α-2a is effective in young female patients. © 2016 The Japan Society of Hepatology.

Changes in peak systolic velocity induced by chronic therapy with phosphodiesterase type-5 inhibitor.

PubMed

Sighinolfi, M C; Mofferdin, A; De Stefani, S; Celia, A; Micali, S; Cicero, A F G; Bianchi, G

2006-06-01

The aim of this study was to assess the influence of chronic therapy with phosphodiesterase type-5 inhibitor on penile haemodynamics at colour Doppler ultrasound. Thirty patients affected by erectile dysfunction (ED) of different aetiology tested with the International Index of Erectile Function (IIEF-5) were evaluated with penile colour Doppler ultrasound during basic and dynamic phases (10 microg PGE1) before and after chronic self-administration of sildenafil citrate (dosage: 100 mg as required, two to three times a week) for a period of 5-20 months (mean: 12.3). Treatment was interrupted 14-21 days before the second ultrasound evaluation. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were recorded by means of colour Doppler; cut off values were 25 and 5 cm s(-1) respectively. Data were compared by nonparametric tests. Twenty-two of the 30 patients showed normal pre-treatment PSV, while eight of 30 had an insufficient arterial flow. Mean pre-treatment EDV was 4.7 +/- 0.5. After chronic therapy with sildenafil, a global improvement of 10.5% on PSV was seen (P < 0.001), without any statistical difference between patients with normal pre-treatment peak and those with a borderline one. No statistically significant changes were found for EDV (P = 0.98). It is concluded that chronic therapy with phosphodiesterase-5 inhibitor results in a significant improvement in PSV values, probably due to a penile chronic vasoactive enhancement.

Determination of salicylic acid by HPLC in plasma and saliva from children with juvenile chronic arthritis.

PubMed

Legaz, M E; Acitores, E; Valverde, F

1992-12-01

A high performance liquid chromatography (HPLC) method has been developed for measuring salicylic acid in the plasma and saliva of children with juvenile chronic arthritis (JCA). Samples were extracted with diethyl ether and, after drying, redissolved in methanol to be chromatographed. Quantitation of salicylic acid was performed by reverse phase HPLC on a spherisorb ODS-2 column, using methanol: water: acetic acid as mobile phase. Phenolic was monitored by absorbance at 237 nm. Linearity between the amount of mass injected and the response in the detector was determined. This method was applied to compare concentrations of salivary and plasma salicylic acid. The method also permitted the quantitation of salivary salicylate as a non-invasive, indirect method for monitoring the concentration of plasma salicylate in patients with JCA.

[How can we improve symptomatic hypotension in hemodialysis patients: cold dialysis vs isothermic dialysis].

PubMed

Ramos, R; Soto, C; Mestres, R; Jara, J; Zequera, H; Merello, J I; Moreso, F

2007-01-01

Symptomatic hypotension is the most frequent acute complication affecting patients during chronic hemodialysis treatment sessions. Many reports have demonstrated that the use of cool dialysate has a protective effect on blood pressure during hemodialysis treatments. In the present study, we investigated whether preventing the hyperthermic response had favourable effects on hemodynamic stability during the hemodialysis procedure while affording good tolerance to patients. We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients in our center. Patients were eligible for the study if they had symptomatic hypotensive episodes (> 3/12session/ month) during the screening phase. The study was designed with two phases for the same selected patients and two treatment arms, each phase lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36 masculineC for 12 sessions (cold dialysis) and in the second phase we used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature unchanged (isothermic dialysis). Nine HD patients were enrolled and completed the study. During the screening phase the mean ultrafiltration was 4 1% of dry weight, and blood pressure decreased from 9916 to 8016 mm Hg (p<0.001). In 5.01.7 sessions of 12 treatments were complicated by hypotension. In the first and second phase we observed a decrease of complicated treatments with symptomatic hypotension (5.01.7 versus 2.71.6 y 2.81.7; p<0.01). Both procedures: Cold dialysis and Isothermic dialysis was well tolerated by patients. Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients.

Modification of hemiplegic compensatory gait pattern by symmetry-based motion controller of HAL.

PubMed

Kawamoto, Hiroaki; Kadone, Hideki; Sakurai, Takeru; Sankai, Yoshiyuki

2015-01-01

As one of several characteristics of hemiplegic patients after stroke, compensatory gait caused by affected limb is often seen. The purpose of this research is to apply a symmetry-based controller of a wearable type lower limb robot, Hybrid Assistive Limb (HAL) to hemiplegic patients with compensatory gait, and to investigate improvement of gait symmetry. The controller is designed respectively for swing phase and support phase according to characteristics of hemiplegic gait pattern. The controller during swing phase stores the motion of the unaffected limb and then provides motion support on the affected limb during the subsequent swing using the stored pattern to realize symmetric gait based on spontaneous limb swing. Moreover, the controller during support phase provides motion to extend hip and knee joints to support wearer's body. Clinical tests were conducted in order to assess the modification of gait symmetry. Our case study involved participation of one chronic stroke patient who performs abnormally-compensatory gait for both of the affected and unaffected limbs. As a result, the patient's gait symmetry was improved by providing motion support during the swing phase on the affected side and motion constraint during the support phase on the unaffected side. The study showed promising basis for the effectiveness of the controller for the future clinical study.

Depressive disorder in the last phase of life in patients with cardiovascular disease, cancer, and COPD: data from a 20-year follow-up period in general practice.

PubMed

Warmenhoven, Franca; Bor, Hans; Lucassen, Peter; Vissers, Kris; van Weel, Chris; Prins, Judith; Schers, Henk

2013-05-01

Depression is assumed to be common in chronically ill patients during their last phase of life and is associated with poorer outcomes. The prevalence of depression is widely varying in previous studies due to the use of different terminology, classification, and assessment methods. To explore the reported incidence of depressive disorder, as registered in the last phase of life of patients who died from cardiovascular disease, cancer or COPD, in a sample of primary care patients. A historic cohort study, using a 20-year period registration database of medical records in four Dutch general practices (a dynamic population based on the Continuous Morbidity Registration database). Medical history of the sample cohort was analysed for the diagnosis of a new episode of depressive disorder and descriptive statistics were used. In total 982 patients were included, and 19 patients (1.9%) were diagnosed with a new depressive disorder in the last year of their life. The lifetime prevalence of depressive disorder in this sample was 8.2%. The incidence of depressive disorder in the last phase of life is remarkably low in this study. These data were derived from actual patient care in general practice. Psychiatric diagnoses were made by GPs in the context of both patient needs and delivered care. A broader concept of depression in general practice is recommended to improve the diagnosis and treatment of mood disorders in patients in the last phase of life.

Circulating MicroRNAs as Potential Biomarkers for Traumatic Brain Injury-Induced Hypopituitarism.

PubMed

Taheri, Serpil; Tanriverdi, Fatih; Zararsiz, Gokmen; Elbuken, Gulsah; Ulutabanca, Halil; Karaca, Zuleyha; Selcuklu, Ahmet; Unluhizarci, Kursad; Tanriverdi, Kahraman; Kelestimur, Fahrettin

2016-10-15

Traumatic brain injury (TBI), a worldwide public health problem, has recently been recognized as a common cause of pituitary dysfunction. Circulating microRNAs (miRNAs) present in the sera are characteristically altered in many pathological conditions and have been used as diagnostic markers for specific diseases. It is with this goal that we planned to study miRNA expression in patients with TBI-induced hypopituitarism. Thirty-eight patients (27 male, 11 female; mean age, 43 ± 18 years) who had been admitted to the neurosurgery intensive care unit due to TBI were included in the acute phase of the study. In the chronic phase, miRNA expression profile blood samples were drawn from 25 patients who had suffered TBI 5 years ago. In the acute phase (on Days 1, 7, and 28), a substantial amount of patients (26%, 40%, and 53%; respectively) had hypopituitarism (acute adrenocorticotropic hormone deficiency). In the chronic phase eight of 25 patients (32%) had TBI-induced-hypopituitarism. Forty-seven age-gender-similar healthy controls (25 male, 22 female, mean age: 41 ± 14 years) were included in the study. In order to identify potential candidate miRNA/miRNAs whose levels had been altered in response to TBI-induced hypopituitarism, 740 miRNA expression analyses were performed in the sera of TBI patients by high throughput real-time polymerase chain reaction. Statistical analyses showed that miRNA-126-3p (miR-126-3p) and miRNA-3610 (miR-3610) were detected in the sera of patients who developed hypopituitarism on the 1st, 7th, and 28th days, and in the 5th year following TBI. In addition, miRNA-3907 showed statistically significant and constant dynamic changes on the 1st, 7th, and 28th days, and in the 5th year in the patients with TBI. Our results indicated that altered expression of miR-126-3p and miR-3610 may play an important role in the development of TBI-induced hypopituitarism.

Lubiprostone: a chloride channel activator for treatment of chronic constipation.

PubMed

Ambizas, Emily M; Ginzburg, Regina

2007-06-01

To review lubiprostone's pharmacology, pharmacokinetics, efficacy, and safety in the treatment of chronic constipation. A literature search was conducted using PubMed/MEDLINE (1966-January 2007), IngentaConnect, and International Pharmaceutical Abstracts (1977-January 2007). Key words used included lubiprostone, Amitiza, and chronic constipation. All articles identified from the data sources that were published in English were evaluated. Lubiprostone is a chloride channel activator approved by the Food and Drug Administration for the treatment of chronic constipation. A randomized, double-blind, parallel-group, placebo-controlled study evaluating the effect of lubiprostone on gastric function showed slowed gastric emptying and increased small bowel and colonic transit time. Peak plasma concentration was shown to be around 1.14 hours, with a majority of the drug excreted in the urine within 48 hours. Phase III trials have noted that most patients with chronic constipation have a spontaneous bowel movement within 24 hours after taking lubiprostone. The most common adverse events in these trials were nausea, diarrhea, abdominal pain, and headache. Lubiprostone use has not been studied in the pediatric population. Lubiprostone may be a reasonable alternative for use in patients who either fail or are intolerant of standard therapy for chronic constipation. Head-to-head comparison studies with conventional therapy are needed to contrast clinical efficacy and safety of this medication.

Deanol in the treatment of tardive dyskinesia.

PubMed

Simpson, G M; Voitashevsky, A; Young, M A; Lee, J H

1977-05-09

Ten hospitalized chronic psychotic patients with symptoms of tardive dyskinesia were given deanol and placebo, each for 8 weeks following a double-bline, crossover design. No psychotropic agents were administered during the trial. Improvement occurred in all patients during the first treatment phase regardless of which drug the patients received; seven patients were on deanol and three on placebo during this time. The possible reasons for this decrease were discussed. It was concluded that deanol may have contributed to the decline but that its effect on the disorder was not dramatic.

Physician involvement in disease management as part of the CCM.

PubMed

Wallace, Paul J

2005-01-01

Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee-for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I.

Physician Involvement in Disease Management as Part of the CCM

PubMed Central

Wallace, Paul J.

2005-01-01

Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee-for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I. PMID:17288075

Sensitivity and specificity of ultrasonographic features of gout in intercritical and chronic phase.

PubMed

Das, Shyamashis; Ghosh, Alakendu; Ghosh, Parasar; Lahiri, Debasish; Sinhamahapatra, Pradyot; Basu, Kaushik

2017-07-01

This study aimed to assess the sensitivity and specificity of ultrasonographic features of gout in intercritical and chronic stages and compared ultrasonographic features of gout between patients with persistent high serum uric acid (SUA) and patients with low SUA. Adult patients with gout confirmed by demonstration of monosodium urate crystals were recruited, if they were in intercritical or chronic stage clinically. Ultrasonographic examination of the first metatarsophalangeal joints (MTPJs) and the knee joints of both sides were done by a blinded rheumatologist trained in musculoskeletal ultrasound. Sixty-two patients with gout and 30 control subjects were examined. The double contour sign (DCS) was found in 71 (57.3%) first MTPJs and tophi were found in 54 (43.5%) first MTPJs. DCS was present in 43 (69.4%) gout patients but none in the control group (P < 0.001). Sensitivity and specificity (95% CI) of DCS in gout patients were 69.4% (56.4-80.4%) and 100% (88.3-100%), respectively, while of tophi they were 66.1% (53-77.7%) and 100% (88.3-100%), respectively. The sensitivity of DCS increased to 100% in high the SUA subgroup (SUA ≥ 7 mg/dL). The low SUA (SUA < 7 mg/dL) gout subgroup showed significantly higher occurrence of erosions (40%) and tophi (50%) in first MTP joints than the control group. MSUS is useful for diagnosis of gout in intercritical or chronic stages, especially in patients with persistently high SUA level. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

PubMed Central

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat Soft Mist Inhaler in patients with asthma and chronic obstructive pulmonary disease.

PubMed

Kässner, Frank; Hodder, Rick; Bateman, Eric D

2004-01-01

Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI. A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800 microg via Respimat SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device. The results of the trials demonstrated that IB/FEN via Respimat SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates the need for a spacer.

HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection.

PubMed

Alexopoulou, Alexandra; Karayiannis, Peter

2014-06-28

Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become "inactive HBsAg carriers". However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients.

[Efficacy of nebulizer therapy with acetylcystein in outpatients with chronic obstructive lung disease].

PubMed

Stepanishcheva, L A; Ignatova, G L; Blinova, E V

2005-01-01

Chronic obstructive lung disease (COLD) is a widespread illness with constantly growing mortality. Mucolytic therapy plays a significant role in treatment of patients with COLD. The paper contains the results of nebulization with acetyl-cystein as part of rehabilitation program in outpatients with stable clinical course of I-II stage of COLD. The results demonstrated significant clinical improvement, as well as positive changes in external respiration parameters (1 sforced expiratory volume), increase of physical activity tolerance, and disappearance of acute inflammation phase reactants in saliva.

Bioelectrical impedance phase angle relates to function, disease severity and prognosis in stable chronic obstructive pulmonary disease.

PubMed

Maddocks, Matthew; Kon, Samantha S C; Jones, Sarah E; Canavan, Jane L; Nolan, Claire M; Higginson, Irene J; Gao, Wei; Polkey, Michael I; Man, William D-C

2015-12-01

Bioelectrical impedance analysis (BIA) provides a simple method to assess changes in body composition. Raw BIA variables such as phase angle provide direct information on cellular mass and integrity, without the assumptions inherent in estimating body compartments, e.g. fat-free mass (FFM). Phase angle is a strong functional and prognostic marker in many disease states, but data in COPD are lacking. Our aims were to describe the measurement of phase angle in patients with stable COPD and determine the construct and discriminate validity of phase angle by assessing its relationship with established markers of function, disease severity and prognosis. 502 outpatients with stable COPD were studied. Phase angle and FFM by BIA, quadriceps strength (QMVC), 4-m gait speed (4MGS), 5 sit-to-stand time (5STS), incremental shuttle walk (ISW), and composite prognostic indices (ADO, iBODE) were measured. Patients were stratified into normal and low phase angle and FFM index. Phase angle correlated positively with FFM and functional outcomes (r = 0.35-0.66, p < 0.001) and negatively with prognostic indices (r = -0.35 to -0.48, p < 0.001). In regression models, phase angle was independently associated with ISW, ADO and iBODE whereas FFM was removed. One hundred and seventy patients (33.9% [95% CI, 29.9-38.1]) had a low phase angle. Phenotypic characteristics included lower QMVC, ISW, and 4MGS, higher 5STS, ADO and iBODE scores, and more exacerbations and hospital days in past year. The proportion of patients to have died was significantly higher in patients with low phase angle compared to those with normal phase angle (8.2% versus 3.6%, p = 0.02). Phase angle relates to markers of function, disease severity and prognosis in patients with COPD. As a directly measured variable, phase angle offers more useful information than fat-free mass indices. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice

PubMed Central

Asmall, Shaidah

2015-01-01

Background South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. Methods The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. Results The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. Conclusion The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process. PMID:26528101

Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice.

PubMed

Mahomed, Ozayr Haroon; Asmall, Shaidah

2015-01-01

South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process.

The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis.

PubMed

Don, Burl R; Spin, Gregory; Nestorov, Ivan; Hutmacher, Matt; Rose, Aubri; Kaysen, George A

2005-11-01

Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-alpha TNF-alpha The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-alpha receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL(-1) and C-reactive protein levels <5 mg L(-1) (five men, one woman, age range 34-59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13-16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose.

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial.

PubMed

Clark, Richard E; Polydoros, Fotios; Apperley, Jane F; Milojkovic, Dragana; Pocock, Christopher; Smith, Graeme; Byrne, Jenny L; de Lavallade, Hugues; O'Brien, Stephen G; Coffey, Tony; Foroni, Letizia; Copland, Mhairi

2017-07-01

Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia with deep molecular responses; however, patients with stable major molecular response (MMR), but not MR4, have not been studied, nor has the effect of treatment de-escalation rather than outright cessation. We aimed to examine the effects of treatment de-escalation as a prelude to complete cessation, not only in patients with MR4 or greater, but also in those with MMR but not MR4. We did this interim analysis of a non-randomised, phase 2 trial at 20 hospitals in the UK. We recruited patients (aged ≥18 years) with chronic myeloid leukaemia in first chronic phase who had received TKI for 3 years or more and were either in stable MR4 (BCR-ABL1:ABL1 ratio <0·01%; MR4 cohort) or in stable MMR (BCR-ABL1:ABL1 ratio consistently <0·1%) but not MR4 (MMR cohort) for 12 months or longer. Participants received half their standard TKI dose (imatinib 200 mg daily, dasatinib 50 mg daily, or nilotinib 200 mg twice daily) for 12 months. Molecular recurrence was defined as loss of MMR (BCR-ABL1:ABL1 ratio >0·1%) on two consecutive samples. The primary endpoint of this interim analysis was the proportion of patients who lost MMR on de-escalation and regained MMR on TKI resumption. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01804985. Between Dec 16, 2013 and April 10, 2015, we enrolled 174 patients into the MMR cohort (n=49) or the MR4 cohort (n=125). During the 12 months of half-dose therapy, 12 patients (7%) had molecular recurrence, all of whom regained MMR within 4 months of full-dose TKI resumption (median time to recovery 77 days). Recurrence was significantly lower in the MR4 cohort (three [2%; 90% CI 0·2-4·8] of 121 evaluable patients) than in the MMR cohort (nine [19%; 90% CI 9·5-28·0] of 48 evaluable patients; hazard ratio 0·12, 90% CI 0·04-0·37; p=0·0007), but was unrelated to previous TKI or TKI therapy duration. Adverse events (eg, lethargy, diarrhoea, rash, and nausea) improved during the first 3 months of de-escalation, though not thereafter. 16 serious adverse events were reported, including one fatality due to worsening pre-existing peripheral arterial occlusive disease in a patient who had received only imatinib. TKI de-escalation is safe for most patients with excellent responses to TKI therapy, and is associated with improvement in symptoms. These findings show that lower TKI doses might maintain responses in these patients, implying that such patients could be unnecessarily overtreated. Studies of more ambitious de-escalation are warranted. Newcastle University and Bloodwise. Copyright © 2017 Elsevier Ltd. All rights reserved.

Routine Sub-hepatic Drainage versus No Drainage after Laparoscopic Cholecystectomy: Open, Randomized, Clinical Trial.

PubMed

Shamim, Muhammad

2013-02-01

Surgeons are still following the old habit of routine subhepatic drainage following laparoscopic cholecystectomy (LC). This study aims to compare the outcome of subhepatic drainage with no drainage after LC. This prospective study was conducted in two phases. Phase I was open, randomized controlled trial (RCT), conducted in Civil Hospital Karachi, from August 2004 to June 2005. Phase II was descriptive case series, conducted in author's practice hospitals of Karachi, from July 2005 to December 2009. In phase I, 170 patients with chronic calculous cholecystitis underwent LC. Patients were divided into two groups, subhepatic drainage (group A: 79 patients) or no drainage (group B: 76 patients). The rest 15 patients were excluded either due to conversion or elective subhepatic drainage. In phase II, 218 consecutive patients were enrolled, who underwent LC with no subhepatic drainage. Duration of operation, character, and amount of drain fluid (if placed), postoperative ultrasound for subhepatic collection, postoperative chest X-ray for the measurement of subdiaphragmatic air, postoperative pain, postoperative nausea/vomiting, duration of hospital stay, and preoperative or postoperative complications were noted and analyzed. Duration of operation and hospital stay was slightly longer in group A patients (P values 0.002 and 0.029, respectively); postoperative pain perception, nausea/vomiting, and postoperative complications were nearly same in both groups (P value 0.064, 0.078, and 0.003, respectively). Subhepatic fluid collection was more in group A (P = 0.002), whereas subdiaphragmatic air collection was more in group B (P = 0.003). Phase II results were nearly similar to group B patients in phase I. Routine subhepatic drainage after LC is not necessary in uncomplicated cases.

Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia.

PubMed

Mohty, Mohamad; Szydlo, Richard M; Yong, Agnes S M; Apperley, Jane F; Goldman, John M; Melo, Junia V

2008-09-01

Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a "high" level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.

Disappearance of Ph1 chromosome with intensive chemotherapy and detection of minimal residual disease by polymerase chain reaction in a patient with blast crisis of chronic myelogenous leukemia.

PubMed

Honda, H; Miyagawa, K; Endo, M; Takaku, F; Yazaki, Y; Hirai, H

1993-06-01

We diagnosed a patient with chronic myelogenous leukemia (CML) in chronic phase (CP) on the basis of clinical findings, Ph1 chromosome detected by cytogenetic analysis, and bcr-abl fusion mRNA detected by reverse transcriptase-dependent polymerase chain reaction (RT-PCR). One month after diagnosis, the patient developed extramedullary blast crisis in the lymph nodes, and then medullary blast crisis in the bone marrow, in which different surface markers were shown. Combination chemotherapy with BH-AC, VP16, and mitoxantrone was administered; this resulted in rapid disappearance of the lymphadenopathy, restoration of normal hematopoiesis, and no Ph1 chromosome being detected by cytogenetic analysis. RT-PCR performed to detect the residual Ph1 clone revealed that although the Ph1 clone was preferentially suppressed, it was still residual. The intensive chemotherapy regimen preferentially suppressed the Ph1-positive clone and led to both clinical and cytogenetic remission in this patient with BC of CML; we suggest that RT-PCR is a sensitive and useful method for detecting minimal residual disease during the clinical course of this disease.

The effects of uncinectomy and natural ostial dilatation on maxillary sinus ventilation: a clinical experimental study.

PubMed

Kutluhan, Ahmet; Şalvız, Mehti; Bozdemir, Kazım; Kanbak, Orhan; Ulu, Mustafa; Yalçıner, Gökhan; Bilgen, Akif Sinan

2011-04-01

The purpose of this study was to determine the effect of uncinectomy without sinusotomy and natural ostial dilatation on maxillary sinus ventilation in chronic rhinosinusitis. Twenty patients with chronic rhinosinusitis were included in this study. The patients were randomly divided into two groups. Group 1 consisted of patients with uncinectomy (n = 10), while group 2 was made up of patients treated with natural ostial dilatation (n = 10). The CO(2) tension and pressure levels of the maxillary sinus during inspiration and expiration phases were obtained and compared before and after the procedures within and between the groups. The mean CO(2) tension levels in both groups were significantly decreased after the procedures. The mean maxillary sinus pressure during inspiration was significantly decreased to a negative value after uncinectomy; however, no significant change was observed during expiration. There were no significant changes in maxillary sinus pressures after natural ostial dilatation procedure. Both uncinectomy and natural ostial dilatation seem to be equally effective in decreasing maxillary sinus pCO(2) levels. The effects of decreased maxillary sinus pressure during inspiration after uncinectomy on mucociliary clearance and development mechanisms of chronic rhinosinusitis seem to be worth investigating.

Peripolesis followed by cytotoxicity in chronic idiopathic inflammatory bowel disease.

PubMed Central

Wilders, M M; Drexhage, H A; Kokjé, M; Verspaget, H W; Meuwissen, S G

1984-01-01

Antigen presenting veiled cells have recently been described in cell suspensions prepared from the gut wall of patients with chronic idiopathic inflammatory bowel disease (CIBD). The normal gut wall is virtually devoid of these cells. In this report we describe a phenomenon known as peripolesis studied by phase contrast cinematography. This is a process in which lymphocytes are seen to wander around larger target cells. These could be identified ultrastructurally as Ia positive veiled cells. In most cases peripolesis was followed by lysis of the target cell. Peripolesis was recorded in cell suspensions of three out of seven patients with ulcerative colitis and in three out of nine patients with Crohn's disease; furthermore peripolesis was observed in one out of two patients with non-classifiable CIBD. In four cell suspensions showing peripolesis, cell lysis could be recorded and was especially striking in ulcerative colitis. Peripolesis involving veiled cells was previously described in delayed hypersensitivity reactions. This study lends support to the concept that delayed allergic reactivity plays a part in chronic inflammatory bowel disease. The antigens involved are, however, completely unknown. Images Fig. 1 Fig. 2 Fig. 3 PMID:6380839

First experience with early dynamic (18)F-NaF-PET/CT in patients with chronic osteomyelitis.

PubMed

Freesmeyer, Martin; Stecker, Franz F; Schierz, Jan-Henning; Hofmann, Gunther O; Winkens, Thomas

2014-05-01

This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using (18)F-sodium fluoride-((18)F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed(18)F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late (18)F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late (18)F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed(18)F-NaF -PET offers additional information about early radiotracer distribution to standard (18)F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed(18)F-NaF-PET to a three-phase bone scan.

Iron-Magnesium Hydroxycarbonate (Fermagate): A Novel Non-Calcium-Containing Phosphate Binder for the Treatment of Hyperphosphatemia in Chronic Hemodialysis Patients

PubMed Central

McIntyre, Christopher W.; Pai, Pearl; Warwick, Graham; Wilkie, Martin; Toft, Alex J.; Hutchison, Alastair J.

2009-01-01

Background and objectives: This phase II study tested the safety and efficacy of fermagate, a calcium-free iron and magnesium hydroxycarbonate binder, for treating hyperphosphatemia in hemodialysis patients. Design, setting, participants, & measurements: A randomized, double-blind, three-arm, parallel-group study compared two doses of fermagate (1 g three times daily or 2 g three times daily with placebo). Sixty-three patients who had been on a stable hemodialysis regimen for ≥3 mo were randomized to the treatment phase. Study medication was administered three times daily just before meals for 21 d. The primary endpoint was reduction in serum phosphate over this period. Results: In the intention-to-treat analysis, mean baseline serum phosphate was 2.16 mmol/L. The fermagate 1- and 2-g three-times-daily treatment arms were associated with statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L, respectively. Adverse event (AE) incidence in the 1-g fermagate arm was statistically comparable to the placebo group. The 2-g arm was associated with a statistically higher number of patients reporting AEs than the 1-g arm, particularly gastrointestinal AEs, as well as a higher number of discontinuations, complicating interpretation of this dose's efficacy. Both doses were associated with elevations of prehemodialysis serum magnesium levels. Conclusions: The efficacy and tolerability of fermagate were dose dependent. Fermagate showed promising efficacy in the treatment of hyperphosphatemia in chronic hemodialysis patients as compared with placebo in this initial phase II study. The optimal balance between efficacy and tolerability needs to be determined from future dose-titration studies, or fixed-dose comparisons of more doses. PMID:19158369

Phase II trial of vindesine in patients with acute leukemia.

PubMed

Sklaroff, R B; Arlin, Z; Young, C W

1979-01-01

Vindesine was administered to 18 patients with acute leukemia who had failed conventional chemotherapy. Each course of therapy consisted of an iv bolus infusion at a dose of 1-2 mg/m2 given daily x 5-10 days. Of 13 patients with acute lymphoblastic leukemia, two had partial remissions which lasted 2 and 3 months and five had minor responses. One of three patients with acute nonlymphoblastic leukemia and one of two patients with blastic crisis of chronic myelogenous leukemia each had a minor response. The data suggest that vindesine has activity in the treatment of acute leukemia.

Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies.

PubMed

Place, Andrew E; Goldsmith, Kelly; Bourquin, Jean-Pierre; Loh, Mignon L; Gore, Lia; Morgenstern, Daniel A; Sanzgiri, Yeshwant; Hoffman, David; Zhou, Ying; Ross, Jeremy A; Prine, Betty; Shebley, Mohamad; McNamee, Megan; Farazi, Thalia; Kim, Su Young; Verdugo, Maria; Lash-Fleming, Leanne; Zwaan, C Michel; Vormoor, Josef

2018-03-29

Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies.

PubMed

Fallon, Marie T; Albert Lux, Eberhard; McQuade, Robert; Rossetti, Sandro; Sanchez, Raymond; Sun, Wei; Wright, Stephen; Lichtman, Aron H; Kornyeyeva, Elena

2017-08-01

Opioids are critical for managing cancer pain, but may provide inadequate relief and/or unacceptable side effects in some cases. To assess the analgesic efficacy of adjunctive Sativex (Δ 9 -tetrahydrocannabinol (27 mg/mL): cannabidiol (25 mg/mL)) in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. This report describes two phase 3, double-blind, randomized, placebo-controlled trials. Eligible patients had advanced cancer and average pain numerical rating scale (NRS) scores ≥4 and ≤8 at baseline, despite optimized opioid therapy. In Study-1, patients were randomized to Sativex or placebo, and then self-titrated study medications over a 2-week period per effect and tolerability, followed by a 3-week treatment period. In Study-2, all patients self-titrated Sativex over a 2-week period. Patients with a ≥15% improvement from baseline in pain score were then randomized 1:1 to Sativex or placebo, followed by 5-week treatment period (randomized withdrawal design). The primary efficacy endpoint (percent improvement (Study-1) and mean change (Study-2) in average daily pain NRS scores) was not met in either study. Post hoc analyses of the primary endpoints identified statistically favourable treatment effect for Sativex in US patients <65 years (median treatment difference: 8.8; 95% confidence interval (CI): 0.00-17.95; p = 0.040) that was not observed in patients <65 years from the rest of the world (median treatment difference: 0.2; 95% CI: -5.00 to 7.74; p = 0.794). Treatment effect in favour of Sativex was observed on quality-of-life questionnaires, despite the fact that similar effects were not observed on NRS score. The safety profile of Sativex was consistent with earlier studies, and no evidence of abuse or misuse was identified. Sativex did not demonstrate superiority to placebo in reducing self-reported pain NRS scores in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy, although further exploration of differences between United States and patients from the rest of the world is warranted.

Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE

PubMed Central

Radbruch, Helena; Bremer, Daniel; Guenther, Robert; Cseresnyes, Zoltan; Lindquist, Randall; Hauser, Anja E.; Niesner, Raluca

2016-01-01

Most multiple sclerosis (MS) patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in MS is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS) macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic MS. Here, we employ intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1–4, DUOX1, 2) and, thus, to identify the cellular source of oxidative stress in the CNS of mice affected by experimental autoimmune encephalomyelitis (EAE) in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET–FLIM, providing a possible mechanism of disease progression in MS. PMID:27014271

Proactive and Early Aggressive Wound Management: A Shift in Strategy Developed by a Consensus Panel Examining the Current Science, Prevention, and Management of Acute and Chronic Wounds.

PubMed

Bohn, Gregory A; Schultz, Gregory S; Liden, Brock A; Desvigne, Michael N; Lullove, Eric J; Zilberman, Igor; Regan, Mary B; Ostler, Marta; Edwards, Karen; Arvanitis, Georgia M; Hartman, Jodi F

2017-11-01

Normal wound healing is accomplished through a series of well-coordinated, progressive events with overlapping phases. Chronic wounds are described as not progressing to healing or not being responsive to management in a timely manner. A consensus panel of multidisciplinary wound care professionals was assembled to (1) educate wound care practitioners by identifying key principles of the basic science of chronic wound pathophysiology, highlighting the impact of metalloproteinases and biofilms, as well as the role of the extracellular matrix; and (2) equip practitioners with a systematic strategy for the prevention and healing of acute injuries and chronic wounds based upon scientific evidence and the panel members' expertise. An algorithm is presented that represents a shift in strategy to proactive and early aggressive wound management. With proactive management, adjunct therapies are applied preemptively to acute injuries to reduce wound duration and risk of chronicity. For existing chronic wounds, early aggressive wound management is employed to break the pathophysiology cycle and drive wounds toward healing. Reducing bioburden through debridement and bioburden management and using collagen dressings to balance protease activity prior to the use of advanced modalities may enhance their effectiveness. This early aggressive wound management strategy is recommended for patients at high risk for chronic wound development at a minimum. In their own practices, the panel members apply this systematic strategy for all patients presenting with acute injuries or chronic wounds.

Mediating the Cognitive Walkthrough with Patient Groups to achieve Personalized Health in Chronic Disease Self-Management System Evaluation.

PubMed

Georgsson, Mattias; Kushniruk, Andre

2016-01-01

The cognitive walkthrough (CW) is a task-based, expert inspection usability evaluation method involving benefits such as cost effectiveness and efficiency. A drawback of the method is that it doesn't involve the user perspective from real users but instead is based on experts' predictions about the usability of the system and how users interact. In this paper, we propose a way of involving the user in an expert evaluation method by modifying the CW with patient groups as mediators. This along with other modifications include a dual domain session facilitator, specific patient groups and three different phases: 1) a preparation phase where suitable tasks are developed by a panel of experts and patients, validated through the content validity index 2) a patient user evaluation phase including an individual and collaborative process part 3) an analysis and coding phase where all data is digitalized and synthesized making use of Qualitative Data Analysis Software (QDAS) to determine usability deficiencies. We predict that this way of evaluating will utilize the benefits of the expert methods, also providing a way of including the patient user of these self-management systems. Results from this prospective study should provide evidence of the usefulness of this method modification.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

PubMed

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-02-01

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. AbbVie Inc and Genentech Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

PubMed Central

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-01-01

Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3–4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66–91) and 89% (95% CI 72–96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. Interpretation A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. PMID:28089635

Upper-limb robot-assisted therapy in rehabilitation of acute stroke patients: focused review and results of new randomized controlled trial.

PubMed

Masiero, Stefano; Armani, Mario; Rosati, Giulio

2011-01-01

The successful motor rehabilitation of stroke patients requires early intensive and task-specific therapy. A recent Cochrane Review, although based on a limited number of randomized controlled trials (RCTs), showed that early robotic training of the upper limb (i.e., during acute or subacute phase) can enhance motor learning and improve functional abilities more than chronic-phase training. In this article, a new subacute-phase RCT with the Neuro-Rehabilitation-roBot (NeReBot) is presented. While in our first study we used the NeReBot in addition to conventional therapy, in this new trial we used the same device in substitution of standard proximal upper-limb rehabilitation. With this protocol, robot patients achieved similar reductions in motor impairment and enhancements in paretic upper-limb function to those gained by patients in a control group. By analyzing these results and those of previous studies, we hypothesize a new robotic protocol for acute and subacute stroke patients based on both treatment modalities (in addition and in substitution).

PTCH1 expression at diagnosis predicts imatinib failure in chronic myeloid leukaemia patients in chronic phase.

PubMed

Alonso-Dominguez, Juan M; Grinfeld, Jacob; Alikian, Mary; Marin, David; Reid, Alistair; Daghistani, Mustafa; Hedgley, Corinne; O'Brien, Stephen; Clark, Richard E; Apperley, Jane; Foroni, Letizia; Gerrard, Gareth

2015-01-01

The tyrosine kinase inhibitor (TKI) imatinib has revolutionized the management of chronic myeloid leukaemia (CML). However, around 25% of patients fail to sustain an adequate response. We sought to identify gene-expression biomarkers that could be used to predict imatinib response. The expression of 29 genes, previously implicated in CML pathogenesis, were measured by TaqMan Low Density Array in 73 CML patient samples. Patients were divided into low and high expression for each gene and imatinib failure (IF), probability of achieving CCyR, progression free survival and CML related OS were compared by Kaplan-Meier and log-rank. Results were validated in a second cohort of 56 patients, with a further technical validation using custom gene-expression assays in a conventional RT-qPCR in a sub-cohort of 37 patients. Patients with low PTCH1 expression showed a worse clinical response for all variables in all cohorts. PTCH1 was the most significant predictor in the multivariate analysis compared with Sokal, age and EUTOS. PTCH1 expression assay showed the adequate sensitivity, specificity and predictive values to predict for IF. Given the different treatments available for CML, measuring PTCH1 expression at diagnosis may help establish who will benefit best from imatinib and who is better selected for second generation TKI. © 2014 Wiley Periodicals, Inc.

Clinical roundtable monograph: Emerging treatment options for TKI-resistant chronic myelogenous leukemia.

PubMed

Cortes, Jorge; Radich, Jerald; Mauro, Michael J

2012-10-01

The development of tyrosine kinase inhibitors (TKIs) that inhibit signaling of the constitutive BCR-ABL protein revolutionized the treatment of chronic myelogenous leukemia (CML). These agents have dramatically changed the treatment landscape for CML, shifting the use of allogeneic stem cell transplantation to selected patients in the salvage setting. Four BCR-ABL TKIs are now commercially available for the treatment of CML: the first-generation TKI imatinib, and the second-generation TKIs dasatinib, nilotinib, and bosutinib. Continuous treatment with these agents induces durable responses in a high proportion of patients with chronic-phase CML. Research is focused on identifying which patients can discontinue therapy without a recurrence of disease. For the group of patients with resistance to TKIs, multiple alternative therapies are being evaluated. The third-generation TKI ponatinib is a BCR-ABL inhibitor that has demonstrated significant activity, including in patients with the TKI resistance mutation T315I. The homoharringtonine derivative omacetaxine mepesuccinate, which inhibits protein synthesis, has also demonstrated clinical activity in CML, including in patients with TKI resistance due to T315I and in patients who have TKI resistance despite no evidence of ABL mutations. It is essential that clinicians implement these new agents with care and change therapies only when appropriate in order to preserve as many options as possible for future use if needed.

Myopathy in CRPS-I: disuse or neurogenic?

PubMed

Hulsman, Natalie M; Geertzen, Jan H B; Dijkstra, Pieter U; van den Dungen, Jan J A M; den Dunnen, Wilfred F A

2009-08-01

The diagnosis Complex Regional Pain Syndrome type I (CRPS-I) is based on clinical symptoms, including motor symptoms. Histological changes in muscle tissue may be present in the chronic phase of CRPS-I. Aim of this study was to analyze skeletal muscle tissue from amputated limbs of patients with CRPS-I, in order to gain more insight in factors that may play a role in changes in muscles in CRPS-I. These changes may be helpful in clarifying the pathophysiology of CRPS-I. Fourteen patients with therapy resistant and longstanding CRPS-I, underwent an amputation of the affected limb. In all patients histological analysis showed extensive changes in muscle tissue, such as fatty degeneration, fibre atrophy and nuclear clumping, which was not related to duration of CRPS-I prior to amputation. In all muscles affected, both type 1 and type 2 fibre atrophy was found, without selective type 2 fibre atrophy. In four patients, type grouping was observed, indicating a sequence of denervation and reinnervation of muscle tissue. In two patients even large group atrophy was present, suggesting new denervation after reinnervation. Comparison between subgroups in arms and legs showed no difference in the number of changes in muscle tissue. Intrinsic and extrinsic muscles were affected equally. Our findings show that in the chronic phase of CRPS-I extensive changes can be seen in muscle tissue, not related to duration of CRPS-I symptoms. Signs of neurogenic myopathy were present in five patients.

Chronic Hepatitis C Treatment in Patients with Drug Injection History: Findings of the INTEGRATE Prospective, Observational Study.

PubMed

Robaeys, Geert; Christensen, Stefan; Lucidarme, Damien; Arain, Amber; Bruggmann, Philip; Kunkel, Jan; Keim, Sofia; Jäkel, Martin; DeMasi, Ralph; Liu, Chris; Lonjon-Domanec, Isabelle; Foster, Graham R

2017-06-01

People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population. INTEGRATE was a prospective, observational study investigating the effectiveness, safety, and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin (Peg-IFN/RBV) in patients with history of injecting drug use chronically infected with genotype 1 HCV. A total of 46 patients were enrolled and included in the intent-to-treat (ITT) population. Among heroin and/or cocaine users (n = 37; 80%), 22% reported use in the past month; 74% (34/46) of patients were on opioid substitution therapy in the pre-treatment phase, and 43% (20/46) discontinued HCV treatment prematurely. Sustained virologic response rate was 54% (25/46) in the ITT population and 74% (25/34) in the per protocol (evaluable-for-effectiveness) population. The main reason for failure in the ITT analysis was loss to follow-up (n = 8; 17%). Adverse events occurred in 91% (42/46) of patients. Mean patient-reported adherence to study drugs was >89% at Week 4, Week 12 and end of treatment. Despite a high rate of treatment discontinuation (including loss to follow-up), self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts. Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection, and highlight the need for improvements in patient support to boost retention in care and, in turn, help to prevent reinfection and transmission. Clinicaltrials.gov identifier, NCT01980290. Janssen Pharmaceuticals.

Inflammatory biomarkers, disease activity index, and self-reported disability may be predictors of chronic arthritis after chikungunya infection: brief report.

PubMed

Sepúlveda-Delgado, J; Vera-Lastra, O L; Trujillo-Murillo, K; Canseco-Ávila, L M; Sánchez-González, R A; Gómez-Cruz, O; Lugo-Trampe, A; Fernández-Salas, I; Danis-Lozano, R; Contreras-Contreras, A; Mendoza-Torres, A; Domínguez-Arrevillaga, S; Mena-Vela, B A; Ocaña-Sibilla, M; Ramirez-Valdespino, J C; Jara, L J

2017-03-01

The chikungunya virus (ChikV) is a reemerging mosquito-borne pathogen that causes disabling chronic arthritis. The relationship between clinical evolution and inflammatory biomarkers in patients with ChikV-induced arthritis has not been fully described. We performed a prospective case series to evaluate the association among joint involvement, self-reported disability, and inflammatory biomarkers. Patients with ChikV infection were followed for 1 year. Joint involvement and self-reported disability were evaluated with disease activity index 28 (DAS-28) and World Health Organization Disablement Assessment Schedule II (WHODAS-II). Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were used as biomarkers. Ten patients with mean age 48 ±15.04 years were included. Symptoms at diagnosis were fever, arthralgias, myalgias, rash, arthritis, nausea, vomiting, and back pain. Polyarticular involvement was present in seven cases. At diagnosis, measures were as follows: DAS-28, 5.08±1.11; WHODAS-II score, 72.3±10.3 %; CRP, 5.09±7.23 mg/dL; ESR, 33.5±17.5 mm/h; RF, 64±21.7 IU/mL; and IL-6, 17.6±10.3 pg/mL. Six patients developed subacute and chronic symptoms. During follow-up, DAS-28 index, WHODAS-II score, ESR, and IL-6 were statistically different in patients with subacute and chronic symptoms compared to those who resolved in the acute phase (p < 0.05). DAS-28 index, WHODAS-II score, and IL-6 were related to chronicity of articular symptoms and could be used as predictors of ChikV-induced arthritis.

Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study

DOE PAGES

Lau, George; Benhamou, Yves; Chen, Guofeng; ...

2016-07-25

In order to shorten the course of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, we examined the antiviral efficacy and safety of 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor–NS5B nucleotide analogue. In this open-label, phase 2a, single centre study, Chinese patients with chronic HCV genotype 1b infection without cirrhosis were randomly allocated by a computer program to one of three treatment groups (sofosbuvir, ledipasvir, and asunaprevir; sofosbuvir, daclatasvir, and simeprevir; or sofosbuvir, daclatasvir, and asunaprevir) until six patients in each group (1:1:1) achieved an ultrarapid virological response (plasma HCV RNAmore » <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2.0). Patients with an ultrarapid virological response received 3 weeks of therapy. Patients who did not achieve an ultrarapid response were switched to sofosbuvir and ledipasvir for either 8 weeks or 12 weeks. Furthermore, the primary endpoint was the proportion of patients with a sustained virological response at 12 weeks (SVR12) after treatment completion, analysed in the intention-to-treat population. All patients who achieved an ultrarapid virological response were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02470858. Between April 5, 2015, and April 15, 2015, 26 eligible patients were recruited. 12 patients were assigned to sofosbuvir, ledipasvir, and asunaprevir; six to sofosbuvir, daclatasvir, and simeprevir; and eight to sofosbuvir, daclatasvir, and asunaprevir. Six patients in each group achieved an ultrarapid virological response (18 [69%]). All patients with an ultrarapid virological response who were given 3 weeks of triple therapy achieved SVR12. The most common adverse events were fatigue (one [17%] of six patients receiving sofosbuvir, ledipasvir, and asunaprevir; one [17%] of six patients receiving sofosbuvir, daclatasvir, and simeprevir; and two [33%] of six patients receiving sofosbuvir, daclatasvir, and asunaprevir) and headache (one [17%] patient in each group). There were no patients who experienced any serious adverse events. In this proof-of-concept study, all patients with chronic HCV without cirrhosis who achieved an ultrarapid virological response on triple direct-acting antiviral regimens by day 2 and received 3 weeks of treatment were cured, with excellent tolerability. By shortening the duration of therapy from the currently recommended 12 weeks to 3 weeks, we could drastically reduce the cost of therapy and the rate of adverse events. Further large-scale studies should be done to confirm our findings.« less

Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, George; Benhamou, Yves; Chen, Guofeng

In order to shorten the course of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, we examined the antiviral efficacy and safety of 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor–NS5B nucleotide analogue. In this open-label, phase 2a, single centre study, Chinese patients with chronic HCV genotype 1b infection without cirrhosis were randomly allocated by a computer program to one of three treatment groups (sofosbuvir, ledipasvir, and asunaprevir; sofosbuvir, daclatasvir, and simeprevir; or sofosbuvir, daclatasvir, and asunaprevir) until six patients in each group (1:1:1) achieved an ultrarapid virological response (plasma HCV RNAmore » <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2.0). Patients with an ultrarapid virological response received 3 weeks of therapy. Patients who did not achieve an ultrarapid response were switched to sofosbuvir and ledipasvir for either 8 weeks or 12 weeks. Furthermore, the primary endpoint was the proportion of patients with a sustained virological response at 12 weeks (SVR12) after treatment completion, analysed in the intention-to-treat population. All patients who achieved an ultrarapid virological response were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02470858. Between April 5, 2015, and April 15, 2015, 26 eligible patients were recruited. 12 patients were assigned to sofosbuvir, ledipasvir, and asunaprevir; six to sofosbuvir, daclatasvir, and simeprevir; and eight to sofosbuvir, daclatasvir, and asunaprevir. Six patients in each group achieved an ultrarapid virological response (18 [69%]). All patients with an ultrarapid virological response who were given 3 weeks of triple therapy achieved SVR12. The most common adverse events were fatigue (one [17%] of six patients receiving sofosbuvir, ledipasvir, and asunaprevir; one [17%] of six patients receiving sofosbuvir, daclatasvir, and simeprevir; and two [33%] of six patients receiving sofosbuvir, daclatasvir, and asunaprevir) and headache (one [17%] patient in each group). There were no patients who experienced any serious adverse events. In this proof-of-concept study, all patients with chronic HCV without cirrhosis who achieved an ultrarapid virological response on triple direct-acting antiviral regimens by day 2 and received 3 weeks of treatment were cured, with excellent tolerability. By shortening the duration of therapy from the currently recommended 12 weeks to 3 weeks, we could drastically reduce the cost of therapy and the rate of adverse events. Further large-scale studies should be done to confirm our findings.« less

Venetoclax Yields Strong Responses in CLL.

PubMed

2016-02-01

Results from an international phase II study show that the investigational BCL2 inhibitor venetoclax is effective in patients with chronic lymphocytic leukemia and the chromosome 17p deletion, whose prognosis is particularly poor. Venetoclax yielded high and durable responses in this population, including several complete remissions. ©2016 American Association for Cancer Research.

A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy

PubMed Central

Awan, Farrukh T.; Jones, Jeffrey A.; Maddocks, Kami; Poi, Ming; Grever, Michael R.; Johnson, Amy; Byrd, John C.; Andritsos, Leslie A.

2016-01-01

Patients with chronic lymphocytic leukemia (CLL) who receive chemoimmunotherapy and do not achieve complete remission experience significantly shortened progression-free interval (PFS). Additionally, the majority of patients treated for relapsed disease demonstrate evidence of measurable disease. Eradication of minimal residual disease (MRD) results in improved PFS and overall survival. Maintenance therapy might result in eradication of MRD and improve response duration but might be associated with an increase in incidence of infectious complications. Flavopiridol is a broad cyclin-dependent kinase (CDK) inhibitor with established safety and efficacy in patients with relapsed CLL, particularly patients with high-risk cytogenetic features. A pharmacologically derived schedule was utilized as consolidation therapy in this phase I study to assess the safety and feasibility of outpatient therapy with flavopiridol in patients with low tumor burden. Flavopiridol was administered as a 30-min loading dose of 30 mg/m2 followed by a 4-h infusion of 30 mg/ m2 once weekly for 3 weeks every 5 weeks (1 cycle) for planned 2 cycles in ten patients. Therapy was extremely well tolerated and no patient developed acute tumor lysis syndrome. The most common toxicities were gastrointestinal. Of the patients, 22 % improved their response from a PR to CR. Eighty-eight percent experienced a reduction in tumor burden as measured by extent of bone marrow involvement including patients with del17p and complex karyotype. The study establishes the safety and efficacy of flavopiridol as consolidation therapy after chemoimmunotherapy for patients with CLL. Further evaluation is required in larger trials for the utility of CDK inhibitors as consolidation or maintenance strategies. Registration number at ClinicalTrials.gov: NCT00377104. PMID:27118540

A phase 2 study of ofatumumab (Arzerra®) in combination with a pan-AKT inhibitor (afuresertib) in previously treated patients with chronic lymphocytic leukemia (CLL).

PubMed

Chen, Christine I; Paul, Harminder; Le, Lisa W; Wei, Ellen N; Snitzler, Susi; Wang, Trina; Levina, Olga; Kakar, Sumeet; Lau, Anthea; Queau, Michelle; Johnston, James B; Smith, Deborah A; Trudel, Suzanne

2018-06-19

AKT plays a centralized role in tumor proliferation and survival and is aberrantly activated in chronic lymphocytic leukemia (CLL). In this phase 2 trial, 30 relapsed/refractory CLL patients were treated with combination afuresertib, a novel oral AKT inhibitor, and ofatumumab for 6 months, followed by afuresertib maintenance for 12 months. We aimed to achieve deeper and more durable responses, without requiring long-term continuous treatment. Treatment was generally well tolerated but respiratory infections were common, with 18% severe requiring hospitalization. Hematologic toxicities were manageable (grade 3-4 neutropenia 39%). At a median follow-up of 13.4 months, overall responses were 50% (complete responses 3.6%). Median progression-free survival was 8.5 months and overall survival 34.8 months. Combination therapy with ofatumumab and afuresertib is active and well tolerated, but does not appear to lead to durable responses and may not provide additional benefit over single-agent ofatumumab in relapsed/refractory CLL. Novel agent combinations are currently undergoing intense investigation.

A Bayesian Approach for Population Pharmacokinetic Modeling of Pegylated Interferon α-2a in Hepatitis C Patients.

PubMed

Saleh, Mohammad I

2017-11-01

Pegylated interferon α-2a (PEG-IFN-α-2a) is an antiviral drug used for the treatment of chronic hepatitis C virus (HCV) infection. This study describes the population pharmacokinetics of PEG-IFN-α-2a in hepatitis C patients using a Bayesian approach. A possible association between patient characteristics and pharmacokinetic parameters is also explored. A Bayesian population pharmacokinetic modeling approach, using WinBUGS version 1.4.3, was applied to a cohort of patients (n = 292) with chronic HCV infection. Data were obtained from two phase III studies sponsored by Hoffmann-La Roche. Demographic and clinical information were evaluated as possible predictors of pharmacokinetic parameters during model development. A one-compartment model with an additive error best fitted the data, and a total of 2271 PEG-IFN-α-2a measurements from 292 subjects were analyzed using the proposed population pharmacokinetic model. Sex was identified as a predictor of PEG-IFN-α-2a clearance, and hemoglobin baseline level was identified as a predictor of PEG-IFN-α-2a volume of distribution. A population pharmacokinetic model of PEG-IFN-α-2a in patients with chronic HCV infection was presented in this study. The proposed model can be used to optimize PEG-IFN-α-2a dosing in patients with chronic HCV infection. Optimal PEG-IFN-α-2a selection is important to maximize response and/or to avoid potential side effects such as thrombocytopenia and neutropenia. NV15942 and NV15801.

Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study.

PubMed

Macdonald, Jamie H; Marcora, Samuele M; Jibani, Mahdi M; Kumwenda, Mick J; Ahmed, Wasim; Lemmey, Andrew B

2007-01-01

In patients with chronic kidney disease (CKD) receiving adequate erythropoietin therapy, the ideal dose of nandrolone decanoate (ND) to enhance muscle mass is not known. In this phase II dose-finding study, 54 patients with CKD stage 5 were randomized to either low, medium or high doses of ND (50, 100 or 200 mg/week for 24 weeks, respectively, in males; doses halved in females), while 7 patients acted as non-randomized controls. The primary outcome measure was appendicular lean mass (ALM) by dual-energy X-ray absorptiometry. Fluid overload (hydration of the fat-free mass) and indicators of physical functioning were secondary measures. Harms were also recorded. Data were analysed using Quade's (1967) non-parametric analysis of covariance. ND increased ALM in a dose-responsive manner (change scores = 0.3 +/- 0.3 vs. 0.8 +/- 0.3 vs. 1.5 +/- 0.5 vs. 2.1 +/- 0.4 kg, control vs. low vs. medium vs. high dose groups, respectively, p < 0.001) with no increases in fluid overload but no consistent effect on physical functioning. The highest dose of ND (100 mg/week) was intolerable in females because of virilizing effects. If goals of future studies are to improve body composition, dosing of ND up to 200 mg/week in males and 50 mg/week in females should be investigated. However, to realize improvements in physical functioning, future phase III trials of ND may require additional interventions such as exercise training. Copyright 2007 S. Karger AG, Basel.

Recovery of BMIPP uptake and regional wall motion in insulin resistant patients following angioplasty for acute myocardial infarction.

PubMed

Fujino, Takayuki; Ishii, Yoshinao; Takeuchi, Toshiharu; Hirasawa, Kunihiko; Tateda, Kunihiko; Kikuchi, Kenjiro; Hasebe, Naoyuki

2003-09-01

The effect of insulin resistance (IR) on the fatty acid metabolism of myocardium, and therefore on the recovery of left ventricular (LV) wall motion, has not been established in patients with acute myocardial infarction (AMI). A total of consecutive 58 non-diabetic AMI patients who had successfully undergone emergency coronary angioplasty were analyzed retrospectively. They were categorized into 2 groups, normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), based on a 75-g oral glucose tolerance test (OGTT). The parameters of OGTT, myocardial scintigraphy (n=58) (thallium-201 (Tl) and iodine-123-beta-methyl-iodophenylpentadecanoic acid (BMIPP)) and left ventriculography (n=24) were compared in the 2 groups after reperfusion (acute phase) and 3-4 weeks after the AMI (chronic phase). The insulin resistance (IR), estimated by the serum concentration of insulin at 120 min (IRI 120') of the OGTT and by the HOMA (the homeostasis model assessment) index, was higher in the IGT group than in NGT group. An inverse correlation was found between the recovery of regional LV wall motion in the ischemic lesion and the IRI 120' and HOMA index. Although the recovery of BMIPP uptake from the acute to the chronic phase was higher in the IGT group, it was only correlated with the degree of IRI 120', not with the HOMA. IR accompanied by IGT can negatively influence the recovery of regional LV wall motion.

Early investigational antibiotics for the treatment of acute exacerbations of chronic bronchitis.

PubMed

Falagas, Matthew E; Georgiou, Maria

2017-03-01

Acute exacerbations in patients with chronic bronchitis are a leading cause of hospitalizations and death. Bacteria contribute significantly to such exacerbations. The aim of this review was to explore the potential role of investigational antibiotics in the treatment of these episodes. Areas covered: The available literature in PubMed database, in websites related to investigational drugs and in websites of the producing companies has been searched. The in vitro activity against pathogens involved in acute exacerbations of chronic bronchitis and the pharmacokinetic profile of antibiotics currently under development were taken into consideration for inclusion in the review. Expert opinion: Several novel antimicrobial agents have completed preclinical and Phase I studies and were well-tolerated. Further investigation is mandatory in order to evaluate their future in treatment of chronic bronchitis exacerbations and discover potential advantages compared to already approved antimicrobials.

Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens.

PubMed

Lin, Katherine I; Tam, Constantine S; Keating, Michael J; Wierda, William G; O'Brien, Susan; Lerner, Susan; Coombes, Kevin R; Schlette, Ellen; Ferrajoli, Alessandra; Barron, Lynn L; Kipps, Thomas J; Rassenti, Laura; Faderl, Stefan; Kantarjian, Hagop; Abruzzo, Lynne V

2009-04-02

Although immunoglobulin V(H) mutation status (IgV(H) MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV(H) somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV(H) MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV(H) than those whose CLL used mutated IgV(H) (TTP 47% vs 82% at 6 years, P < .001). In a multivariate model considering all baseline characteristics, IgV(H) MS emerged as the only determinant of remission duration (hazard ratio 3.8, P < .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgV(H) status.

Advantages of EEG phase patterns for the detection of gait intention in healthy and stroke subjects

NASA Astrophysics Data System (ADS)

Ioana Sburlea, Andreea; Montesano, Luis; Minguez, Javier

2017-06-01

Objective. One use of EEG-based brain-computer interfaces (BCIs) in rehabilitation is the detection of movement intention. In this paper we investigate for the first time the instantaneous phase of movement related cortical potential (MRCP) and its application to the detection of gait intention. Approach. We demonstrate the utility of MRCP phase in two independent datasets, in which 10 healthy subjects and 9 chronic stroke patients executed a self-initiated gait task in three sessions. Phase features were compared to more conventional amplitude and power features. Main results. The neurophysiology analysis showed that phase features have higher signal-to-noise ratio than the other features. Also, BCI detectors of gait intention based on phase, amplitude, and their combination were evaluated under three conditions: session-specific calibration, intersession transfer, and intersubject transfer. Results show that the phase based detector is the most accurate for session-specific calibration (movement intention was correctly detected in 66.5% of trials in healthy subjects, and in 63.3% in stroke patients). However, in intersession and intersubject transfer, the detector that combines amplitude and phase features is the most accurate one and the only that retains its accuracy (62.5% in healthy subjects and 59% in stroke patients) w.r.t. session-specific calibration. Significance. MRCP phase features improve the detection of gait intention and could be used in practice to remove time-consuming BCI recalibration.

Values and preferences in oral anticoagulation in patients with atrial fibrillation, physicians' and patients' perspectives: protocol for a two-phase study.

PubMed

Alonso-Coello, Pablo; Montori, Victor M; Solà, Ivan; Schünemann, Holger J; Devereaux, Philipe; Charles, Cathy; Roura, Mercè; Díaz, M Gloria; Souto, Juan Carlos; Alonso, Rafael; Oliver, Sven; Ruiz, Rafael; Coll-Vinent, Blanca; Diez, Ana Isabel; Gich, Ignasi; Guyatt, Gordon

2008-10-27

Oral anticoagulation prevents strokes in patients with atrial fibrillation but, for reasons that remain unclear, less than 40% of all patients with atrial fibrillation receive warfarin. The literature postulates that patient and clinician preferences may explain this low utilization. The proposed research seeks to answer the following questions: i) When assessed systematically, do patients' and clinicians' preferences explain the utilization of warfarin to prevent strokes associated with atrial fibrillation? ii) To what extent do patients' and clinicians' treatment preferences differ? iii) What factors explain any differences that exist in treatment preferences between patients and clinicians? To answer these questions we will conduct a two-phase study of patient and clinician preferences for health states and treatments. In the first phase of this study we will conduct structured interviews to determine their treatment preferences for warfarin vs. aspirin to prevent strokes associated with atrial fibrillation using the probability trade-off technique. In the same interview, we will conduct preference-elicitation exercises using the feeling thermometer to identify the utilities that patients place on taking medication (warfarin and aspirin), and on having a mild stroke, a severe stroke, and a major bleed. In the second phase of the study we will convene focus groups of clinicians and patients to explore their answers to the exercises in the first phase. This is a study of patient and clinician preferences for health states and treatments. Because of its clinical importance and our previous work in this area, we will conduct our study in the clinical context of the decision to use antithrombotic agents to reduce the risk of stroke in patients with non-valvular chronic atrial fibrillation.

Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir.

PubMed

Younossi, Zobair M; Stepanova, Maria; Gordon, Stuart; Zeuzem, Stefan; Mann, Michael P; Jacobson, Ira; Bourliere, Marc; Cooper, Curtis; Flamm, Steven; Reddy, K Rajender; Kowdley, Kris; Younossi, Issah; Hunt, Sharon

2018-04-01

Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12). We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period. There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0-100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05). In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Personal history and quality of life in chronic myeloid leukemia patients: a cross-sectional study using narrative medicine and quantitative analysis.

PubMed

Breccia, Massimo; Graffigna, Guendalina; Galimberti, Sara; Iurlo, Alessandra; Pungolino, Ester; Pizzuti, Michele; Maggi, Alessandro; Falzetti, Franca; Capalbo, Silvana Franca; Intermesoli, Tamara; Maffioli, Margherita; Elena, Chiara; Melosi, Alessandro; Simonetti, Federico; Capochiani, Enrico; Seta, Roberta Della; Pacilli, Matteo; Luppi, Mario; Di Renzo, Nicola; Mastrullo, Lucia; Trabacchi, Elena; Vallisa, Daniele; Rapezzi, Davide; Orlandi, Ester Maria; Gambacorti-Passerini, Carlo; Efficace, Fabio; Alimena, Giuliana

2016-11-01

Tyrosine kinase inhibitors (TKIs) drastically changed the outcome of patients diagnosed with chronic myeloid leukemia (CML). Several reports indicated the advantage of continue long-term adherence associated with positive outcome. Therefore, it is important to better understand from the patient's standpoint the experience of living with the disease and the related treatment. In this study, quantitative analysis and narrative medicine were combined to get insights on this issue in a population of 257 patients with CML in chronic phase treated with TKIs (43 % men, with a median age of 58 years, 27 % aged 31-50 years), followed for a median time of 5 years. Sixty-one percent of patients enrolled were treated in first line, whereas 37 % were treated in second line. The results showed more positive perceptions and acceptance in males compared to females, without impact of disease on relationships. Level of positive acceptance was more evident in elderly compared to younger patients, with a close connection with median time from diagnosis. Overall, female patients reported negative perceptions and an impact of disease on family daily living. The majority of patients understood the importance of continue adherence to treatment, with 27 % resulting less adherent (60 % for forgetfulness), even if well informed and supported by his/her physician. Narrative medicine, in association to quantitative analysis, can help physicians to understand needs of their patients in order to improve communication.