Influence of age on the correlations of hematological and biochemical variables with the stability of erythrocyte membrane in relation to sodium dodecyl sulfate

Objectives

To evaluate the influence of age on the relationships between biochemical and hematological variables and stability of erythrocyte membrane in relation to the sodium dodecyl sulfate (SDS) in population of 105 female volunteers between 20 and 90 years.

Methods

The stability of RBC membrane was determined by non-linear regression of the dependency of the absorbance of hemoglobin released as a function of SDS concentration, represented by the half-transition point of the curve (D₅₀) and the variation in the concentration of the detergent to promote lysis (dD).

Results

There was an age-dependent increase in the membrane stability in relation to SDS. Analyses by multiple linear regression showed that this stability increase is significantly related to the hematological variable red cell distribution width (RDW) and the biochemical variables blood albumin and cholesterol.

Discussion

The positive association between erythrocyte stability and RDW may reflect one possible mechanism involved in the clinical meaning of this hematological index.     

Incidence of internal tandem duplications and D835 mutations of FLT3 gene in chronic myeloid leukemia patients from Southern India

Objective

To screen two important FLT3 mutations (internal tandem duplication (ITD) and D835 point mutations) in chronic myeloid leukemia (CML) patients from Southern India and report their incidence.

Methods

Screened 350 CML patients and 350 controls for the two FLT3/mutations through polymerase chain reaction and restriction fragment length polymorphism methods.

Results

ITDs were detected in 12 of the 350 CML patients (3.4%) and D835 mutations in only four cases (1.14%), relatively low in frequency as compared to those reported earlier from non-Indian populations. None of the cases showed simultaneous occurence of both ITD and D835 mutations.

Discussion

These FLT3 mutations seem to be very rare in CML, and it is possible that these could be found only in a subset of patients who are in the progressive stage and/or with varied drug response. Prospective studies are needed to confirm the role of FLT3 mutations in CML pathogenesis, which may help devising therapeutic interventions.     

Productivity loss of Japanese patients with rheumatoid arthritis – A cross-sectional survey

Objective: The objective of this study was (1) to determine productivity costs due to absenteeism and presenteeism among Japanese workers with rheumatoid arthritis (RA), and (2) to identify additional factors associated with productivity loss among workers with RA.

Methods: An online survey of 500 RA Japanese patients was used. The Japanese version of the Stanford Health Assessment Questionnaire (J-HAQ) was used to measure patients’ functional disability. The patient health questionnaire-9 item (PHQ-9) was used to measure symptoms and severity of depression. To assess work productivity the ‘work productivity and activity impairment questionnaire’ for rheumatoid arthritis (WPAI-RA), a six-item validated instrument was used.

Results: Percentages of absenteeism and presenteeism were found to be 1% and 23%, respectively. The annual combined productivity costs of both absenteeism and presenteeism was 7877 USD per patient. Factors significantly associated with a higher productivity loss were functional disability, depressive symptoms, and time since RA diagnosis, while age, and biological disease-modifying antirheumatic drugs (bDMARDs) treatment were significantly associated with a lower productivity loss.

Conclusion: Treatment of RA with bDMARDs would likely result in decreased productivity loss among Japanese patients.     

Heterogeneity in clinical course of EBV-associated lymphoproliferative disorder after allogeneic stem cell transplantation

Objective and Importance

Post-transplant lymphoproliferative disorder (PTLD) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associated with Epstein–Barr virus (EBV).

Clinical presentations

Among 263 individuals treated with allo-HSCT for severe aplastic anemia, pure white cell aplasia, T-prolymphocytic leukemia, and relapsed Hodgkin lymphoma, we diagnosed EBV-PTLD in 5 patients. Median age was 29 years (range 19–70 years) and four of five patients were EBV-seropositive prior to HSCT. All five had unrelated EBV-positive donors. In all cases, PTLD occurred within the first year post-transplant (median 4 months).

Intervention

There were two rapidly fatal courses with extensive organ involvement. Both patients showed lymphopenia and thrombocytopenia. In contrast, the three surviving patients had higher lymphocytes and normal platelet counts, while PTLD was restricted to one site and resolved after 2–4 cycles of rituximab.

Conclusion

In this case series courses of PTLD showed substantial diversity.     

Health assessment questionnaire-disability index (HAQ-DI) score at the start of biological disease-modifying antirheumatic drug (bDMARD) therapy is associated with radiographic progression of large joint damage in patients with rheumatoid arthritis

Objectives: Radiographic progression of damage (RPD) to large joints in patients with rheumatoid arthritis (RA) has not been fully studied. We previously demonstrated that Larsen grade of the large joints was associated with RPD of large joints in patients treated with biological disease-modifying anti-rheumatic drugs (bDMARDs); however, no factors associated with background characteristics of patients were identified.

Methods: A total of 400 large joints in the upper and lower extremities, including the shoulder, elbow, knee, and ankle, of 88 patients with RA treated with bDMARDs for 1–3 years were investigated. Radiographs of tender and/or swollen large joints were acquired at least twice during the study period (mean, 16.4 months), and the RPD was evaluated.

Results: A multivariate analysis revealed that health assessment questionnaire-disability index (HAQ-DI) score at the start of bDMARD treatment was associated with RPD. The cutoff value that discriminated progression from non-progression, determined by a receiver operating characteristic (ROC) curve, was 1.4375 (sensitivity: 0.778, specificity: 0.894).

Conclusions: HAQ-DI score at the start of bDMARD treatment was associated with RPD to large joints during a therapeutic period of 1–3 years. Progressive damage is expected to increase when functional disability exceeds an HAQ-DI score of 1.5.     

Low-dose rituximab in the treatment of acquired haemophilia

Objective and importance

Acquired haemophilia is a rare hemorrhagic disease caused by inhibitory autoantibodies against coagulation factor VIII. Rituximab has become a popular choice for immunosuppressive therapy in acquired haemophilia, almost with the same schedule of 375 mg/m² per week for 4–6 doses. While the effect of low-dose rituximab has seldom been reported.

Clinical presentation

We report a patient, aged 88 years, who developed acquired haemophilia with severe hemorrhage and elevation of carbohydrate antigen 125 (CA125), but in the absence of a detectable cause.

Intervention

We prescribed a low-dose rituximab alone (100 mg per week for a total of four infusions) for the patient, different from the conventional usage, but received a similar effect. In addition, the patient was diagnosed with immune thrombocytopenia 22 months after rituximab, while FVIII activity and activated partial thromboplastin time remained within the normal range. After four infusions of low-dose rituximab, the platelet count recovered.

Conclusion

At a follow-up of 34 months, the patient remains in remission without further treatment, suggesting low-dose rituximab seems to be a safe and effective regimen for the elderly patients with acquired haemophilia.     

‘Reflex’ HPLC testing as a screening modality for variant hemoglobins: A pilot study of 1310 cases at a pediatric referral hospital

Objective

High-performance liquid chromatography (HPLC) has been evaluated as useful technique for detection of variant hemoglobins in newborn screening, ethnicity-based screening, and patients with abnormal hemoglobin electrophoresis. This study aimed at evaluating this technique as ‘reflex’ testing in a pediatric referral center.

Methods

This study included 1317 children visiting the pediatric hospital, who underwent HPLC analysis on anticoagulated blood samples. These patients were divided into clinician-requisitioned HPLC (group A), ‘reflex’ testing for anemia (group B), and unrelated etiologies (group C). HPLC graphs were evaluated for various hemoglobins. Statistical analysis was performed for comparison between these groups for frequency of abnormal HPLC assay and various red cell parameters.

Results

The frequency of abnormal HPLC assay was 22.89% in group A (125 of 546 cases), 26.89% in group B (78 of 290 cases), and 31.8% in group C (153 of 781 cases) with statistically significant difference. The most frequent variant in all three groups was thalassemia trait. Thalassemia intermedia and major, both were detected in few patients in groups B and C.

Conclusion

‘Reflex’ testing for hemoglobin variants can be undertaken for pediatric samples to enhance detection of these variants and avoid an additional venepuncture.     

Identifying Cognitive Impairment in Hospitalized Older Adults to Prevent Readmission: Two Case Studies

Objective: To describe two patient outcomes post-discharge from an acute hospital admission. Both patients underwent cognitive testing during hospitalization.

Methods: A battery of cognitive tests was administered to two hospitalized older adult patients. Both patients were evaluated in their homes within 72 hours of discharge and again at 14- and 30-days by a nurse practitioner.

Results: One of the patients was readmitted within 30 days of hospital discharge due to complications from an amputation. This patient did not perform well on cognitive measures which may have been related to his pain levels and/or his medication regimen.

Conclusions: Not all readmissions are avoidable; however, if readmissions are related to cognitive impairment, implementing strategies tailored to this population may reduce readmission rates.

Clinical Implications: Risk factors for readmission should be identified so the discharge team can develop a tailored plan of care. Including both the patient and an informal caregiver may reduce the chance of a hospital readmission in older adults with cognitive impairment regardless of the etiology.     

Acquired hemophilia A: a review of recent data and new therapeutic options

Objectives: Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function.

Methods: We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments.

Results: The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently.

Conclusion: The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.     

Switching from originator to biosimilar infliximab – real world data of a prospective 18 months follow-up of a single-centre IBD population

Background and aims: Long-term data regarding switching from originator infliximab to biosimilar CT-P13 are sparse. Concerns about increased immunogenicity after switching have been raised. We aimed to study the effectiveness, safety and immunogenicity after switching from originator infliximab to CT-P13 in a real-world IBD population with 18 months prospective follow-up.

Methods: All adult IBD patients treated with originator infliximab at the Department of Gastroenterology, Oslo University Hospital, were switched to CT-P13 and followed prospectively for 18 months.

The primary endpoints were (i) the proportion of patients remaining on CT-P13 18 months after switching and (ii) immunogenicity during 18 months after switching. The secondary endpoints included (i) adverse events, (ii) changes in disease activity, C-reactive protein, anaemia, faecal calprotectin, infliximab dose and interval and p-infliximab.

Results: In total, 143 IBD patients were switched, 99 with Crohn’s disease and 44 with ulcerative colitis. Altogether, 130 (91%) remained on CT-P13 throughout 18 months.

Two patients developed ADAs at moderate level and discontinued CT-P13. Another 10 patients discontinued CT-P13 (two due to loss of response without ADAs, four due to adverse events, and four in remission and a personal wish to stop).

There was no overall change in disease activity scores or in the other studied variables except for p-infliximab, which increased significantly.

Conclusions: The present study provides valuable evidence for the safety and effectiveness of switching from originator to biosimilar infliximab over a prolonged period of 18 months and demonstrates that switching was well tolerated and did not affect the long term clinical outcome.     

CpG island methylator phenotype and its relationship with prognosis in adult acute leukemia patients

Objective

To investigated the relationship between CpG island methylator phenotype (CIMP) and prognosis in adults with acute leukemia.

Methods

Bone marrow samples from 53 acute myeloid leukemia and 50 acute lymphoblastic leukemia patients were collected. The methylation status of 18 tumor suppressor genes was determined using methylation-specific polymerase chain reaction.

Results

Greater than 30% of acute leukemia patients had methylated p15, p16, CDH1, CDH13, RUNX3, sFRP1, ID4, and DLC-1 genes; methylation of ≥4 were defined as CIMP positive. Age, type of leukemia, white blood cell count, and CIMP status were significantly associated with recurrence-free survival (RFS) and overall survival (OS) (P < 0.05). CIMP status was an independent prognostic factor for OS (hazard ratio: 2.07, 95% confidence interval: 1.03–4.15, P = 0.040). CIMP-negative patients had significantly improved RFS and OS (P < 0.05). p16 and DLC1 methylation was significantly associated with RFS and OS (P < 0.05).

Conclusions

CIMP may serve as an independent risk factor for evaluating the prognosis of patients with acute leukemia.     

The intensive care management process in patients with hematopoietic stem cell transplantation and factors affecting their prognosis

Objectives

Hematopoietic stem cell transplantation (HSCT) recipients may require further management in intensive care unit (ICU). The ICU outcome of the HSCT recipients is claimed to have improved significantly over the last two decades. Our aim was to investigate the ICU outcome of the HSCT recipients who required management in ICU, together with the factors that are likely to affect the results.

Materials and methods

We retrospectively investigated the ICU outcome of 48 adults (≥18 years of age) who received HSCT in the bone marrow transplant unit of our hospital and required admission to ICU between 01 January 2007 and 31 December 2010. The data were retrieved from the databases of the adult bone marrow transplantation unit and the ICU.

Results

Sixty-one percent of the patients were male with a median age of 39 years (28–46.75) in the study cohort. Leukemia (54%) and lymphoma (27%) were the leading underlying disorders. The type of HSCT was autologous in 14.6% and allogeneic in 85.4% of the patients. The reason for admission to ICU was acute respiratory failure in 85.5% of the HSCT recipients and 75% had sepsis/septic shock. The mean duration of ICU stay was 104.5 (48–168) hours. Sixty-nine percent of the patients died during their ICU stay while 31% survived. Besides the several statistically significant differences between the patients who survived or died in ICU in univariate analysis, baseline Acute Physiology and Chronic Health Evaluation (APACHE II) score (odds ratio 1.38, 95% confidence interval: 1.06–1.79) and requirement of vasopressors in the ICU (odds ratio 72.29, 95% confidence interval:4.47–1169.91) were found to be independent risk factors for mortality in multivariate analysis.

Conclusion

Baseline APACHE II score and requirement of vasopressors during ICU stay were the most significant independent risk factors for mortality in HSCT recipients who required ICU management in our center.     

Recombinant human lipocalin 2 acts as an antibacterial agent to prevent platelet contamination

Background

Bacterial contamination of platelet products is the major infectious risk in blood transfusion medicine, which can result in life-threatening sepsis in recipient. Lipocalin 2 (Lcn2) is an iron-sequestering protein in the antibacterial innate immune response, which inhibit bacterial growth. This study was aimed to evaluate the antibacterial property of Lcn2 in preventing bacterial contamination of platelets.

Methods

Recombinant Lcn2 was expressed in a eukaryotic expression system and following purification and characterization of the recombinant Lcn2, its minimum inhibitory concentration was determined. Then, platelet concentrates were inoculated with various concentrations of Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterococcus faecalis, and the antibacterial effects of Lcn2 was evaluated at 20–24°C.

Results

Results revealed that Lcn2 effectively inhibited the growth of 1.5 × 10⁴ CFU/ml S. epidermidis, P. aeruginosa, K. pneumoniae, E. coli, and E. faecalis at 40 ng/ml. At this concentration, Lcn2 also inhibited the growth of 1.5 × 10³ CFU/ml Staphylococcus aureus and Proteus mirabilis.

Conclusion

Recombinant Lcn2 inhibited growth of a variety of platelet-contaminating bacteria. Therefore, supplementation of platelet concentrates with Lcn2 may reduce bacterial contamination.     

Fear of Falling Restricts Activities of Daily Living after Total Hip Arthroplasty: A One-Year Longitudinal Study

Objectives: To determine the prevalence and time course in changes regarding the fear of falling and whether there are consequent restrictions in activities of daily living (ADL) after total hip arthroplasty (THA).

Methods: This is 1-year longitudinal observational study. We recruited ninety-eight patients before and after THA. Fear of falling was assessed for 12 ADLs preoperatively and postoperatively at 3, 6, and 12 months following THA. In addition, we asked patients to answer whether they had refrained from performing each ADL because of fear of falling.

Results: Fifty-two patients were enrolled for the analysis. The total fear of falling score during ADLs decreased with time after THA. The ADLs in which many patients (over 20%) felt fear even at 12 months were using the stairs (25%), sitting and standing from the floor (23%), and walking around the neighborhood (21%). Approximately 10% of patients were restricted in performing ADLs, such as sitting and standing from the floor, because of fear.

Conclusions: Patients undergoing THA frequently experience fear of falling during some ADLs even at 1 year after the operation, which could cause ADL restrictions.

Clinical Implications: Clinicians should evaluate fear of falling and institute rehabilitation programs individually to decrease excessive fear that might lead to ADL restrictions.     

Molecular and clinical analysis of haemoglobin Lepore in Campania,a region of Southern Italy

Objective: To date in Italy, there is paucity on data about the prevalence, clinical and haematological features of patients carrying the haemoglobin (Hb) Lepore variant in homozygous or in association with other haemoglobinopathies.

Methods: Here we report the results of a retrospective analysis on 33 patients from Campania, a region of Southern Italy, historically followed at ‘UOSD Malattie Rare del Globulo Rosso’ of Cardarelli hospital, Naples, Italy.

Results: We described 33 patients carrying the Hb Lepore variant: 21 compound heterozygotes with a common thalassaemia allele, six patients with homozygous state for Hb Lepore, five patients with Hb Lepore/Hb S and one patient with Hb Lepore/Hb Neapolis were identified. All individuals carried haplotype I or V.

Discussion: These thalassaemic patients showed different phenotypes ranging from severe disease with early blood transfusion dependency to moderate form of thalassaemia intermedia. In most cases, thalassaemia mutation type determined the severity of the disease.

Conclusion: A great variability of clinical phenotype among the same genotypes was also observed suggesting the presence of unknown genetic modifiers acting in combination with Hb Lepore.     

Staff Factors Contributing to Family Satisfaction with Long-Term Dementia Care: A Systematic Review of the Literature

Objective: The aim of the present review was to critically evaluate empirical evidence regarding staff factors that contribute to families’ satisfaction with ongoing care provision for their relatives with dementia in long-term care.

Methods: Four databases were systematically searched using search terms informed by the aim of the present systematic review. The resulting 14 relevant articles comprised both qualitative and quantitative studies.

Results: The findings highlighted three broad areas relating to staff factors that appeared to contribute to families’ satisfaction with care provision: family related factors, relating to staff interaction with families; staffing related factors, focusing on staffing organization and composition; and client related factors, focusing on staff interaction with clients and the quality of care provided.

Conclusions: The findings have important implications for care staff and managers working in such settings regarding staffing organization, staff training, recruitment and retention. Future research directions are discussed.

Clinical Implications: Families want consistent, knowledgeable staff that interact well and respond appropriately to the needs of their relative as well as their own needs as family members. Staff training in such settings should therefore focus not only on staff education but also on the importance of establishing effective relationships with both clients and families.     

Psychotherapy Termination Practices with Older Adults: Impact of Patient and Therapist Characteristics

Objectives: The aims of this study were to survey clinicians’ opinions regarding psychotherapy practices in mutual termination with a specified population (depressed older adult outpatients) and to examine the patient and therapist characteristics that may influence such practices.

Methods: We surveyed psychologists’ (N = 96) psychotherapy termination practices, using a hypothetical depressed older adult as a referent, to assess consensus on the appropriateness of various guidelines to termination and to examine whether these differ as a function of patient and therapist characteristics.

Results: Several practices were generally agreed to be “extremely appropriate” when terminating psychotherapy with older adults, including collaborating to determine the end date of treatment and discussing patient growth. Data also indicate that patient factors, such as personality pathology, and therapist factors, such as having an Integrative theoretical orientation were associated with differential endorsement of termination practices. Identification as a geropsychologist or working regularly with older adults were associated with a more cautious approach to termination.

Conclusions: There is substantial consensus regarding many approaches to termination, but modifications might be appropriate depending on patient characteristics.

Clinical Implications: Clinicians agree on a set of fundamental termination practices when working with older adults, but modify these based on orientation and diagnosis.     

Neighborhood Socioeconomic Status and Cognitive Trajectories in a Diverse Longitudinal Cohort

Objectives: Although individual-level socioeconomic status is associated with poor outcomes, less is known regarding how the social context might affect cognitive outcomes. We examined the effect of neighborhood socioeconomic status (NSES) on baseline cognitive function and trajectories of decline.

Methods: The sample (N = 480) came from a longitudinal cohort recruited to study cognitive function. Mixed effects models examined the influence of NSES on baseline and rate of change in executive function, semantic memory, and episodic memory.

Results: NSES was positively associated with semantic memory scores at baseline, but not with executive function or episodic memory in adjusted models, nor was it associated with cognitive change in longitudinal analyses. In exploratory analyses, for individuals with dementia, those with higher NSES declined faster in executive function and semantic memory than did those with lower NSES.

Conclusions: Results suggest that NSES has limited effects independent of personal characteristics; however, findings showed a complex relation of NSES and decline, with NSES effects observed only for individuals with dementia. Results are discussed in the context of cognitive reserve.

Clinical Implications: Clinical assessments of individuals who present with cognitive impairment might benefit from an understanding of the neighborhood context from which patients come.     

Revisiting beta thalassemia intermedia: past,present, and future prospects

Background: The spectrum of thalassemias is wide ranging from thalassemia minor, which consists of mild hypochromic microcytic anemia without obvious clinical manifestations, to thalassemia major (TM), which is characterized by severe anemia since the first years of life and is transfusion dependent. Thalassemia intermedia (TI) describes those patients with mild or moderate anemia.

Objective: To describe the genetic features and major clinical complications of TI, and the therapeutic approaches available in the management of this disease.

Methods: Publications from potentially relevant journals were searched on Medline.

Results and discussion: Over the past decade, the understanding of TI has increased with regard to pathophysiology and molecular studies. It is now clear that clinical presentation and specific complications make TI different from TM. It is associated with greater morbidity, a wider spectrum of organ dysfunction and more complications than previously thought.

Conclusion: TI is not a mild disease. The interplay of three hallmark pathophysiologic factors (ineffective erythropoiesis, chronic anemia, and iron overload) leads to the clinical presentations seen in TI. New treatment modalities are currently being investigated to broaden the options available for TI management.     

Telephone-Delivered Cognitive-Behavioral Therapy for Older,Rural Veterans with Depression and Anxiety in Home-Based Primary Care

Objectives: Rural, homebound older adults are at increased risk for anxiety and depression and have limited access to mental health services. These individuals face many barriers to receiving evidence-based mental health treatment and would benefit from interventions that increase access to and efficiency of care. The aim of this study was to evaluate use of a telephone-delivered, modular, cognitive behavioral therapy (CBT) intervention for both late-life depression and anxiety delivered to rural, homebound Veterans.

Methods: Three cases are presented to illustrate the flexible adaptation of the intervention for use among older Veterans enrolled in home-based primary care, with varying symptom presentations and functional limitations. The Veterans received 7 to 9 sessions of the CBT intervention, with ordering of skill modules based on symptom presentation and determined collaboratively between patient and therapist.

Results: The three Veterans showed improvement in depression and/or anxiety symptoms following treatment and provided positive feedback regarding their experiences in this program.

Conclusions: These results suggest that telephone-delivered CBT is acceptable to older adults and can be tailored to individual patient needs.

Clinical Implications: Clinicians should consider telephone-delivered CBT as an alternate mode of therapy to increase access to mental health care for rural, homebound individuals with depression and anxiety.