Comparison of analgesic consumption of hemophilic and non-hemophilic patients in knee arthroplasty.

BACKGROUND: Hemophilia is a rare hereditary bleeding disorder that develops as a result of factor VIII or IX deficiency. Long-term complications of hemophilia such as arthropathy, synovitis, and arthritis can lead to the development of recurrent chronic pain. Pain is therefore a critical aspect of hemophilia. The gold standard treatment for end-stage hemophilic knee arthropathy is total knee arthroplasty (TKA). The hypothesis of this study was that after knee replacement surgeries that cause severe post-operative pain, hemophilia patients with chronic analgesic consumption may experience higher levels of pain than non-hemophilic patients, and use more opioid and non-opioid drugs. METHODS: This retrospective study included 82 patients who were hemophilic and non-hemophilic TKA patients operated under general anesthesia. Seventy-three patients were evaluated and divided into two groups according to the diagnosis of hemophilia: 36 patients were investigated in the hemophilic group and 37 patients in the non-hemophilic group. RESULTS: Post-operative tramadol consumption (p=0.002) and pethidine consumption (p=0.003) were significantly higher in the group hemophilia. The length of stay in the hospital was also significantly longer in the hemophilic group (p=0.0001). CONCLUSION: In the light of these informations, we think that acute post-operative pain management of hemophilia patients should be planned as personalized, multimodal preventive, and pre-emptive analgesia.

Desires vs. conditions: A qualitative study exploring the factors affecting the place of death of child with cancer in Turkey.

OBJECTIVE: The purpose of this study was to describe factors affecting the place of death of children with cancer at the end of life. METHODS: The descriptive phenomenological approach was used. Eighteen mothers who lost their children to cancer participated in in-depth interviews. Data were analysed using MAXQDA software version. Codes and categories were developed inductively from participants' narratives. RESULTS: The factors affecting the place of death of children were categorised into two main themes: (1) desires and (2) conditions. Most of the mothers reported that their deceased children wanted to be with their families at the end of life and they wanted to go home. The conditions related to health services were defined as the barriers to the death of their children in the places of death preferred by the mothers. CONCLUSION: The desire to be close to the child was the main factor affecting the parents' decisions. The findings revealed the prevailing circumstances in the death place decision beyond parental desires. These were the child's health conditions, physical conditions of hospitals, and the lack of home care and paediatric palliative care services, which were factors related to the system, and the lack of other options for parents.

Persons With Hemophilia of Generation Y and Their Relatives Attitudes and Expectations From Treatment.

This multicenter cohort study aimed to determine the attitudes and expectations of persons with hemophilia of Generation Y (PwH-Y) toward hemophilia and its treatment comparatively with the opinions of their non-hemophiliac relatives. The study was representative regarding quota-control variables of hemophiliacs registered to the provincial representatives of the Hemophilia Society of Turkey in 4 geographic regions and Istanbul. Sixty-four PwH-Y (62 males) and their 56 first-degree relatives (17 males; Generation X/baby boomers) were interviewed face-to-face using mixed data collection method. "Focus Group Study" method was used for qualitative data. Treatment adherence, requirements, and social activities were questioned with a semi-structured form. Treatment adherence rate of the PwH-Y (46.2%) was lower than that perceived by their relatives (71.4%) (p ≤ 0.05). Vascular access problems were the most common reasons for non-adherence (60% in PwH-Y and 25% in relatives). Among the components the hemophiliacs and their relatives needed most, support for accessibility of drugs/treatment ranked first (41.1% and 45%, respectively), followed by emotional support (26.1% and 32.5%, respectively). For increasing treatment success in PwH-Y, treatment should be personalized and shaped based on personal requirements.

Impact of the HEAD-US Scoring System for Observing the Protective Effect of Prophylaxis in Hemophilia Patients: A Prospective, Multicenter, Observational Study

Objective: This study aimed to observe the preventive effect of prophylactic treatment on joint health in people with hemophilia (PwH) and to investigate the importance of integration of ultrasonographic examination into clinical and radiological evaluation of the joints. Materials and Methods: This national, multicenter, prospective, observational study included male patients aged ≥6 years with the diagnosis of moderate or severe hemophilia A or B from 8 centers across Turkey between January 2017 and March 2019. Patients were followed for 1 year with 5 visits (baseline and 3th, 6th, 9th, and 12th month visits). The Hemophilia Joint Health Score (HJHS) was used for physical examination of joints, the Pettersson scoring system was used for radiological assessment, point-of-care (POC) ultrasonography was used for bilateral examinations of joints, and the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score was used for evaluation of ultrasonography results. Results: Seventy-three PwH, of whom 62 had hemophilia A and 11 had hemophilia B, were included and 24.7% had target joints at baseline. The HJHS and HEAD-US scores were significantly increased at the 12th month in all patients. These scores were also higher in the hemophilia A subgroup than the hemophilia B subgroup. However, in the childhood group, the increment of scores was not significant. The HEAD-US total score was significantly correlated with both the HJHS total score and Pettersson total score at baseline and at the 12th month. Conclusion: The HEAD-US and HJHS scoring systems are valuable tools during follow-up examinations of PwH and they complement each other. We suggest that POC ultrasonographic evaluation and the HEAD-US scoring system may be integrated into differential diagnosis of bleeding and long-term monitoring for joint health as a routine procedure.

Clinical characteristics, late effects and outcomes in pineoblastomas in children: a single center experience.

BACKGROUND: Pineoblastomas (PB) are rare tumors of the central nervous system and are more common in children. There is no consensus about standard of care. The objective of this study is to analyze the outcome of children with PB. METHODS: Six patients with PB who were diagnosed between 1990-2012 were evaluated retrospectively. Demographics, age of diagnosis, first complaint, tumor region, diagnosis type, seeding metastasis to the spinal axis or cerebrospinal fluid (CSF), treatment and survival of these patients were recorded. RESULTS: Three patients had subtotal resection and all patients received chemotherapy and craniospinal irradiation (CSI) after diagnosis. Median follow-up after treatment was 5.5 (range:1-19) years. Two patients are alive with no evidence of disease for 7.5 and 10 years, one of whom was diagnosed with papillary thyroid carcinoma 9.5 years after treatment. One of the patients who died had lived for 19 years after diagnosis. CONCLUSIONS: Pineoblastomas are rare but very aggressive tumors; more effective treatment strategies are needed. Survivors should be followed up for late effects such as second malignancies and endocrine deficiencies.

Acute Complications and Survival Analysis of Childhood Acute Lymphoblastic Leukemia: A 15-year Experience.

BACKGROUND: We evaluated the acute complications that occurred during the treatment of childhood acute lymphoblastic leukemia (ALL) and documented the survival rates of children with ALL. MATERIALS AND METHODS: We retrospectively evaluated 110 children with a diagnosis of ALL treated with the Children's Oncology Group protocol from 1999 to 2014. The demographic, clinical, and laboratory data of 110 patients and acute complications of eligible and evaluable 105 patients were recorded. RESULTS: Of the 110 patients, 65 were male and 45 were female. The mean age at admission was 8.3 ± 5.2 years. Ninety-seven patients (88.2%) had been diagnosed with pre-B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. Of the 110 patients, 40 (36.3%) were in the standard-risk group and 70 (63.7%) were in high-risk group. Of the 110 patients, 105 had been followed up regularly and evaluated for acute complications. Infection was the most common complication (n = 93; 88.5%), followed by gastrointestinal (n = 29; 27.6%), neurologic (n = 28; 26.6%), metabolic/endocrine (n = 16; 15.2%), drug-related hypersensitivity (n = 16; 15.2%), avascular necrosis (n = 13; 12.3%), thrombotic (n = 11; 10.4%), severe psychiatric (n = 2; 1.9%), and various other (n = 12; 11.4%) complications. Of the 110 patients, 98 were assessed in terms of survival analysis. The 5- and 10-year overall survival rates were both 85.9% (standard error [SE], 3.6%). The relapse-free survival rates at 1, 3, and 5 years were 97.9% (SE, 1.5%), 91.3% (SE, 3%), and 86.3% (SE, 3.7%), respectively. CONCLUSION: Childhood ALL, although categorized as curable malignancy owing to the improvements in treatment strategies in recent years, can cause acute complications affecting various systems. Thus, patients should be treated and followed up by multidisciplinary medical teams with high expertise.

A Challenge for Hemophilia Treatment: Hemophilia and Cancer.

BACKGROUND: The risk of developing cancer increases with age and also adverse environmental conditions. The same holds true in the aging people with hemophilia (PwH). Furthermore, cancer is an important challenge for physicians working in multidisciplinary hemophilia care centers. AIM: Here, the authors report 7 hemophiliacs with malignancies diagnosed and managed at our center. STUDY DESIGN: Hemophilia A and B were included. METHOD: Patients with mild, moderate, or severe hemophilia A or B, who were followed-up in our center between January 1999 and December 2018 were included in the study. A total of 470 PwH (391 Hemophilia A and 79 Hemophilia B) were followed in this time period. RESULTS: With a minimum 1 and maximum 20 years (median: 11.5 y) of the following time, 7 of 470 (1.48%) PwH were diagnosed with cancer. The diagnosed cancer types were acute lymphoblastic leukemia, acute myeloid leukemia, thyroid cancer, rectum cancer, malign melanoma, basal cell carcinoma, and gastric cancer. All patients except patients with leukemia had major surgical intervention and the hemostasis control was provided on the basis of institutional protocols. At the end of the study, all of the patients were alive besides the patient with acute myeloid leukemia. CONCLUSIONS: Nowadays, the management of PwH has improved immensely and the life span has progressively become similar to healthy male individuals. For accurate improvement and standardizing care, prospective data collection on the epidemiology of cancer in PwH is an important tool.

Efficacy of tolterodine in children with overactive bladder.

AIM: Tolterodine is an anticholinergic drug used for the treatment of overactive bladder. We evaluated the effects of tolterodine on clinical symptoms and compared its efficacy with that of oxybutynin in terms of bladder capacity, bladder wall thickness, and post-void residual volume in children with overactive bladder. MATERIAL AND METHODS: Twenty-six patients who were treated with tolterodine for overactive bladder (20 girls, mean age 8.0±2.2 years) were evaluated retrospectively. Twenty patients with overactive bladder who had undergone oxybutynin treatment (15 girls, mean age 7.6±1.8 years) served as the control group. Dysfunctional voiding symptom scoring was used to evaluate the clinical response to tolterodine. To investigate the effect of treatment on the bladder, ultrasonographic data at baseline and the third month were compared with the oxybutynin group. RESULTS: The dysfunctional voiding symptom scores significantly decreased after the third month of tolterodine treatment (p<0.001). Bladder capacity significantly increased (p<0.001), and filled bladder wall thickness decreased (p=0.007); however, post-void residual volumes significantly increased (p<0.001) at the third month. No serious adverse effects were recorded during tolterodine treatment. The increase in bladder capacity at the third month in the tolterodine group was similar to that in the oxybutynin group (p=0.77), but the decrease in filled bladder wall thickness was significantly greater in the tolterodine group (p=0.019). CONCLUSION: Tolterodine remarkably ameliorates the clinical symptoms of overactive bladder in a short time, and seems to be as effective as oxybutynin for the treatment of overactive bladder in children. Its effect on reduction of bladder wall thickness appears to be superior to that of oxybutynin.

Evaluation of Chromogenic Factor VIII Assay Compared with One-Stage Clotting Assay.

BACKGROUND: Congenital factor VIII (FVIII) deficiency causes hemophilia A due to different types of defects in the FVIII gene. Although the chromogenic measurement is the reference method and shows less variability, a one-stage assay is the most commonly preferred method for measurement of FVIII. In this study, we aimed to evaluate the analytical performances of chromogenic and one-stage assays, and compare the results prior to introduction of newly developed extended half-life recombinant FVIII products. METHODS: Sixty-six blood samples from residual material of Istanbul Faculty of Medicine, Central Laboratory workflow comprised the study group. Samples were classified; plasma FVIII > 40 IU and FVIII < 40 IU. FVIII activities were measured using one-stage clotting and chromogenic assays on a CS-2500 analyzer. Analytical performances were determined through precision, linearity, carryover, and comparability studies. RESULTS: The within-run CV% of the one-stage assay on the CS-2500 had 1.6%, 2.6%, the between day CV% were 8.5%, 4.9 % for low and high controls, respectively. The within-run CV% of chromogenic method had 1.2% and 0.9%. Both methods demonstrated good linearity (R2 > 0.998), and the comparisons of both assays exhibited good agreement with minor bias for FVIII activity > 40 IU. However, a significant bias was obtained for FVIII activity < 40 IU. CONCLUSIONS: We obtained higher results using the one-stage assay compared with the chromogenic assay, and a significant bias was found for the samples lower than 40 IU. The discrepancy can explained by the presence of a weak agreement for samples lower than 10 IU due to the lower detection limit of the chromogenic assay used in this study (1.5%).

Prognostic factors of radiosynovectomy in haemophilia patients with inhibitors: Survival analysis in a 19-year period.

INTRODUCTION: People with haemophilia (PwH) with inhibitors have an increased risk of bleeding and early development of progressive arthropathy. Radiosynovectomy (RS) has been effective in dramatically reducing the frequency of haemarthroses. In the present study, the mid- and long-term results of the efficacy of RS in PwHs with inhibitors and prognostic factors that influence success and failure of RS were presented. MATERIAL AND METHOD: Radiosynovectomy was performed in 51 joints of 22 PwHs with inhibitors diagnosed with chronic haemophilic synovitis between January 2000 and December 2018. Two patients were lost to follow-up and four joints were excluded. Number of bleeding episodes within the pre- and post-treatment 6 months were documented. Treatment failure was defined as need for repeat RS injection. RESULTS: Results of 47 RS were analysed. The mean bleeding frequency of the joints was 11.2 ± 6.2 (median 9) within the last 6 months in the pre-treatment evaluation. After the treatment, the mean bleeding frequency of the joints decreased to 1.2 ± 2.8 (median 0) for first 6 months (P < .0001). The cumulative survival rate at 12 months was 87% and 78% at 36 months. The receiver operating characteristic (ROC) curve analysis revealed that cut-off points of 12 bleeding episodes within the last 6 months (sensitivity, 71.4; specificity, 81.8 P = .0022) and an inhibitor titre of 63.4 BU (sensitivity, 57.1; specificity, 75.8; P = .31) were threshold levels for a predisposition for failure. CONCLUSION: Radiosynovectomy is an effective and safe intervention in PwHs with inhibitors. Bleeding frequency is a prognostic marker for the success of RS treatment. Patients who have more than 12 bleeding episodes within the last 6 months before the RS treatment have a higher rate of failure.

Burkitt Leukemia With Precursor B-Cell Immunophenotype and Dual Translocation of t(14;18) and t(8;14) in a Child: Case Report and Review of the Literature.

BACKGROUND: Burkitt leukemia (BL) with the precursor B-cell immunophenotype is a rarely reported condition. The prognosis of such patients is similar to that of classic BL. However, the combination of chromosomal translocations associated with bcl-2 and c-myc rearrangement has a poor prognosis. OBSERVATIONS: An 11-year-old child presented with fever and weakness. Bone marrow aspiration showed morphologically L1 type blasts and flow cytometry analysis was compatible with precursor B-cell immunophenotype. Cytogenetic analysis revealed a combination of t(8;14) and t(14;l8). CONCLUSIONS: The combination of t(8;14) and t(14;l8) can exhibit different immunophenotypical and morphologic features in leukemias.

Low-dose Immune Tolerance Induction in Hemophilia: A Single-Center Experience.

INTRODUCTION: The development of inhibitors against factors VIII/IX is the most serious complication in hemophilia. The best treatment strategy for inhibitor eradication is immune tolerance induction (ITI). The aim of this study was to evaluate patients treated with low-dose ITI at a single center with limited resources. MATERIALS AND METHODS: In total, 29 (8.05%) of 360 hemophilia A patients exhibited inhibitors. The data from hemophilia patients with inhibitors undergoing ITI between 1999 and 2017 were collected and analyzed. RESULTS: Seventeen ITIs administered to 15 hemophilia A patients with inhibitors were analyzed, and the data from 13 ITIs conducted in 12 patients were evaluated. The median age at ITI onset was 10 years (range: 1.25 to 52 y). The maximum inhibitor titer before ITI was 30 Bethesda Units (BU) (range: 4.48 to 135), and the median inhibitor titer was 1.25 BU (range: 0 to 5.6) at the onset of ITI. The median time interval between the inhibitor development and ITI onset was 60 months (range: 7 to 264 mo). The median inhibitor titer during ITI was 3.4 BU (range: 0 to 158.7). At the end of the treatment, 4 of the 12 patients (33.3%) exhibited a complete response, 4 (33.3%) had partial responses (with continuing ITI), and 4 (33.3%) exhibited ITI failure. CONCLUSIONS: Treatment of hemophilia patients with inhibitors is challenging, and ITI is the best treatment method; however, a high-dose daily ITI regimen cannot be given to every patient in every country due to its high cost. Our results show that low-dose ITI may be a choice for selected patients with inhibitors.

Evaluation of Unfavorable Cardiovascular and Metabolic Risk Factors in Children and Young Adults with Haemophilia

Objective: Increased risk of unfavorable cardiovascular risk factors has been recognised in ageing patients with haemophilia (PwH), but needs further studies in younger patients. The purpose of this study was to assess obesity, hypertension (HT), metabolic variables, insulin resistance and metabolic syndrome in young PwH. Methods: Forty-eight haemophilia A and B patients and 35 age and sex matched healthy controls were included in the study. Anthropometric measurements, blood pressure (BP), fasting glucose and insulin levels, serum lipids and diet were evaluated. The metabolic syndrome was defined according to the criteria of the International Diabetes Federation for pediatric and adult age groups. Results: The mean age of PwH was 21±9 years (range, 6-40 years). Of those ≥18 years, 46% were were obese/overweight while there were no obese/overweight cases in the <18 year-old patients. Obesity was more prevalent in PwH with arthropathy (p=0.017). Seven percent of the PwH between 10 and 18 years-old and 25% of those ≥18 years had metabolic syndrome. There was no difference in metabolic syndrome frequency between PwH and controls >10 years-old (19.5% vs 10% respectively, p=0.34). Fifty percent of the PwH ≥18 years-old had elevated BP or HT. Fasting blood glucose levels of PwH were significantly higher compared to controls (p=0.02). Conclusion: Our study showed that obesity, HT and metabolic syndrome are frequent problems, especially in PwH with arthropathy. Early prevention and management of overweight, obesity and their sequelae must be addressed in clinical practice in order to maximize the overall health of the haemophilia population.

Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis.

This is the report of a 2-year-old boy who presented with fever, cytopenia, and splenomegaly. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) and treated with HLH-2004 protocol. Repeated bone marrow aspiration showed amastigotes on follow-up. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis to avoid chemotherapy toxicity.

Heterogeneity of sleep quality in relation to circadian preferences and depressive symptomatology among major depressive patients.

BACKGROUND: The current study aimed at investigating the latent dimensional structure of sleep quality as indexed by the seven components of the Pittsburgh Sleep Quality Index (PSQI), as well as latent covariance structure between sleep quality, circadian preferences and depressive symptoms. METHODS: Two hundred twenty-five patients with major depressive disorder (MDD), with an average age of 29.92 ±â€¯10.49 years (aged between 17 and 63), participated in the study. The PSQI, Morningness-Eveningness Questionnaire (MEQ) and Beck Depression Inventory (BDI) were administered to participants. Four sets of latent class analyses were subsequently run to obtain optimal number of latent classes best fit to the data. RESULTS: Mixture models revealed that sleep quality is multifaceted in MDD. The data best fit to four-latent-class model: Poor Habitual Sleep Quality (PHSQ), Poor Subjective Sleep Quality (PSSQ), Intermediate Sleep Quality (ISQ), and Good Sleep Quality (GSQ). MDD patients classified into GSQ latent class (23.6%) reported the lowest depressive symptoms and were more prone to morningness diurnal preferences compared to other three homogenous sub-groups. Finally, the significant association between eveningness diurnal preferences and depressive symptomatology was significantly mediated by poor sleep quality. LIMITATION: The cross-sectional nature of the study and the lack of an objective measurement of sleep such as polysomnography recordings was the most striking limitation of the study. CONCLUSIONS: We concluded sleep quality in relation to circadian preferences and depressive symptoms has a heterogeneous nature in MDD.

Variant Guillain-Barré syndrome in a patient with Hodgkin lymphoma: AMSAN.

Lymphomas are solid tumors characterized by the malignant proliferation of lymphoid cells. Neurologic signs encountered in patients with Hodgkin's lymphoma can be due to the direct spread of tumor to the nervous system, secondary to chemotherapy or radiation, secondary to tumor mass compression, infectious causes and paraneoplastic syndromes. Paraneoplastic neurologic syndromes are rarely encountered in patients with Hodgkin's lymphoma and non-Hodgkin's lymphoma. Except for paraneoplastic cerebellar degeneration in Hodgkin's lymphoma and dermato/polymyositis in both Hodgkin's lymphoma and non-Hodgkin's lymphoma, other paraneoplastic syndromes are uncommon and have only been reported as isolated case reports or short series. Here, we present a patient with Hodgkin's lymphoma with symptoms of bilateral lower extremity weakness and loss of sensation before the start of therapy, who was eventually diagnosed as having motor and sensory axonal neuropathy.

The effects of individual biological rhythm differences on sleep quality, daytime sleepiness, and dissociative experiences.

Individuals who differ markedly by sleep chronotype, i.e., morning-type or evening-type also differ on a number of psychological, behavioral, and biological variables. Among several other psychological functions, dissociation may also lead to disruption and alteration of consciousness, which may facilitate dream-like experiences. Our study was aimed at an inquiry into the effects of individual biological rhythm differences on sleep quality and daytime sleepiness in conjunction with dissociative experiences. Participants were 372 undergraduate college students, completed a package of psychological instruments, including the Morningness-Eveningness Questionnaire, Dissociative Experiences Scale, Insomnia Severity Index, and Epworth Sleepiness Scale. Using logistic regression models, direct relations of pathological dissociation with sleepiness, sleep quality and circadian preferences were investigated. Poor sleep quality and sleepiness significantly contributed to the variance of dissociative symptomatology. Although there was no substantial linear association between circadian preferences and pathological dissociation, having evening-type preferences of sleep was indirectly associated with higher dissociation mediated by poor sleep quality. Poor sleep quality and daytime sleepiness seems to be significant antecedents of pathological dissociation. Sleep chronotype preferences underlie this relational pattern that chronobiological characteristics seem to influence indirectly on dissociative tendency via sleep quality.