Impact of pain and functional impairment in US adults with haemophilia: Patient-reported outcomes and musculoskeletal evaluation in the pain, functional impairment and quality of life (P-FiQ) study.

INTRODUCTION: Standardized and disease-specific patient-reported outcome (PRO) instruments assessing pain, functional impairment and health-related quality of life (HRQoL) in people with haemophilia (PWH) have been used in studies, but infrequently in comprehensive care settings for individual assessment or treatment planning. AIM: To assess the impact of pain and functional impairment on HRQoL in PWH. METHODS: P-FiQ enrolled 381 adult PWH with a history of joint pain/bleeding and included 5 PROs and a clinical joint evaluation (Hemophilia Joint Health Score v2.1 [HJHS]). RESULTS: Median age was 34 years; 49.9% reported a history of joint procedure or surgery. On EQ-5D-5L, most reported problems with mobility (61.4%), usual activities (53.2%) and pain/discomfort (76.1%). On Brief Pain Inventory v2 Short Form, median worst pain (range 0-10) was 6, least pain 1, average pain 3 and current pain 2. Ankles were most frequently reported as the most painful joints (37.4%), followed by knees (23.7%) and elbows (18.9%). On International Physical Activity Questionnaire, 51% reported no activity in the prior week. On SF-36v2 health survey, median subscores were worse for 4 physical health domains vs 4 mental health domains. Among Hemophilia Activities List domains (range 0 [worst]-100 [best]), functions of the legs (median, 66.7) and lying/sitting/kneeling/standing (median, 67.5) were most impacted and self-care least impacted (median, 100.0). On HJHS, ankle scores (median, 6.0; range, 0-40) were worse than elbow/knee scores (median, 4.0/4.0). Results were consistent across PROs/HJHS. CONCLUSION: Data demonstrate challenges of predominantly ankle/knee pain and lower extremity functional impairment in US adult PWH, affecting HRQoL across PROs/HJHS.

Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

INTRODUCTION: Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain. AIM: To assess self-reported prevalence, description and management of pain in adult males with mild-to-severe haemophilia and history of joint pain/bleeding. METHODS: Participants completed a pain survey and five patient-reported outcome instruments assessing pain, functional impairment and health-related quality of life (HRQoL). RESULTS: Of 381 participants enrolled, median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65% were overweight/obese. Many (56%) were not receiving routine infusions; 30% never received routine infusions. During the prior 6 months, 20% experienced acute pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed (30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti-inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice (65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common opioid for both acute/chronic pain (30%); other long-acting opioids were infrequently used specifically for chronic but not acute pain (morphine, 7%; methadone, 6%; fentanyl patch, 2%). CONCLUSION: Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused.

US experience with recombinant factor VIIa for surgery and other invasive procedures in acquired haemophilia: analysis from the Hemostasis and Thrombosis Research Society Registry.

INTRODUCTION: Acquired haemophilia (AH) is a rare disorder caused by autoantibodies against factor VIII. AIM: The Hemostasis & Thrombosis Research Society (HTRS) Registry was used to monitor the safety of recombinant FVII (rFVIIa). This study aims to report data from the HTRS Registry regarding safety and efficacy of rFVIIa for haemostatic management of surgeries and other invasive procedures in patients with AH. METHODS: For each rFVIIa-treated procedure, the initial dose, total dose, average infused dose, number of doses and treatment duration were calculated. Efficacy was assessed on a 4-point scale. RESULTS: Of 166 registered patients with AH, 37 patients underwent 58 procedures [30 (51%) rFVIIa-treated]. The median (range) age of all patients undergoing procedures was 70 (13-93) years; for rFVIIa-treated patients, 74 (28-89) years. Approximately 67% (39/58) of all procedures were elective. Overall, the most common procedures were endoscopy (12) and central venous access device (10); rFVIIa was used preoperatively (11), postoperatively (13) and during six follow-up procedures during ongoing postoperative rFVIIa treatment. The median (range) initial dose was 90.0 (44-187) µg kg(-1) preoperatively and 106.0 (56-270) µg kg(-1) postoperatively. For rFVIIa-treated episodes with a reported outcome, 20 (91%) were rated excellent/good or no additional agents used and 2 (9%) were rated as poor/ineffective requiring a switch to another bypassing agent. No thromboembolic events were reported. CONCLUSIONS: Adequate haemostasis was provided for 91% of rFVIIa-treated procedures at doses largely conforming to the package insert. No safety concerns were reported.

Safety of recombinant activated factor VII (rFVIIa) in patients with congenital haemophilia with inhibitors: overall rFVIIa exposure and intervals following high (>240 µg kg⁻¹) rFVIIa doses across clinical trials and registries.

Recombinant activated factor VII (rFVIIa) is indicated for treatment of bleeding in congenital haemophilia with inhibitors (CHwI) using 90 µg kg(-1) every 2-3 h (EU and US) or a single 270 µg kg(-1) dose (EU only) with ~90% efficacy reported for both regimens. Dosing of rFVIIa varies, and home treatment makes assessment of frequency of doses >90 µg kg(-1), the intervals before additional treatment, and the risk for thromboembolic events (TEs) more difficult. This post hoc analysis assessed the safety and distribution of rFVIIa dosing in CHwI and the impact of >240 µg kg(-1) dosing on subsequent bypassing agent (BPA) dosing interval and frequency. Data regarding on-demand or prophylactic rFVIIa dosing, TE incidence and subsequent BPA dosing after high rFVIIa doses were compiled from multiple sources incorporating safety surveillance. A total of 61 734 rFVIIa doses were reported in 481 patients treated for 3947 bleeds and for 43 135 prophylaxis days. Over half (52%) exceeded 120 µg kg(-1), 37% exceeded 160 µg kg(-1) and 15% exceeded 240 µg kg(-1). Subsequent doses of BPA(s) were administered after 38% of initial and 49% of any rFVIIa dose >240 µg kg(-1), and were most frequently administered ≥24 h after initial (40%) or any (53%) doses >240 µg kg(-1). No TEs were reported. The findings of this analysis show that rFVIIa doses >90 µg kg(-1) are utilized for 'real-world' treatment of children and adults. When additional BPA was administered following an rFVIIa dose >240 µg kg(-1), reported intervals were prolonged, often ≥24 h. No safety issues were identified in the 61,734 doses analysed.

Dosing and effectiveness of recombinant activated factor VII (rFVIIA) in congenital haemophilia with inhibitors by bleed type and location: the experience of the Haemophilia and Thrombosis Research Society (HTRS) Registry (2004-2008).

Control of bleeding in patients with congenital haemophilia with inhibitors requires use of bypassing agents such as recombinant activated factor VII (rFVIIa). Due to the difficulties in performing prospective clinical trials in this small subgroup of patients with haemophilia and the need for postmarketing surveillance, a large-scale database was developed by the Hemophilia and Thrombosis Research Society. This report comprises an analysis of the database with respect to assessing dosing and efficacy of rFVIIa by bleed type and location. Between January 2004 and November 2008, data from 129 inhibitor patients with 2041 rFVIIa-treated bleeds were analysed. The bleeds were primarily spontaneous (58%) and traumatic (30%). The most common locations were joints (57%), muscle (20%), mucosal (7%) and subcutaneous (6%). Median total rFVIIa doses per bleeding episode for spontaneous and traumatic bleeds were 540 mcg kg(-1) (4 injections/2 days) and 300 mcg kg(-1) (2.5 injections/1 day) respectively. Median total rFVIIa dose (mean dose, number of injections) was 480 mcg kg(-1) (110 mcg kg(-1) , 3) for joint; 557 mcg kg(-1) (120 mcg kg(-1) , 4) for muscle; 360 mcg kg(-1) (120 mcg kg(-1) , 3) for mucosal and 402 mcg kg(-1) (117 mcg kg(-1) , 3) for subcutaneous. Overall efficacy ranged from 89% to 93%; bleeding stopped in 89% of spontaneous and 93% of traumatic bleeds, 90% of joint bleeds, and 89% of muscle, mucosal,and subcutaneous bleeds. Although spontaneous bleeds require slightly higher doses than traumatic bleeds, most bleeds were treated with a median of 3-4 injections (110-130 mcg kg(-1) ). Effectiveness of rFVIIa was consistently high across bleeding types and locations.

Patient/caregiver-reported recombinant factor VIIa (rFVIIa) dosing: home treatment of acute bleeds in the Dosing Observational Study in Hemophilia (DOSE).

Patients with congenital haemophilia with inhibitors experience acute bleeds managed with bypassing agents, such as recombinant FVIIa (rFVIIa). Home-based treatment and dosing patterns in the US remain poorly described. This study aimed to assess the prescribed and actual rFVIIa dosing in frequently bleeding inhibitor patients (≥4 bleeds in 3 months) prescribed first-line therapy with rFVIIa. Patients or caregivers recorded daily diaries, including the details of all bypassing agent infusions for 3-6 months. Median (range) initial rFVIIa dose prescribed for joint, muscle and other bleeds was 167.5 (61.0-289.0) mcg kg(-1). Additional rFVIIa doses prescribed were 90 (61-270) mcg kg(-1) at an interval of 2.5-3 (1-24) h. The actual initial rFVIIa dose reported by patients/caregivers for 158 bleeds was 212 (59-400) mcg kg(-1), with total dose per episode of 695 (74-21257) mcg kg(-1). Patient/caregiver-reported average dose per bleed was 146 (40-400) mcg kg(-1) across 5 (1-106) infusions. The initial rFVIIa dose was higher for haemarthrosis (223 [59-400] mcg kg(-1)) than muscle bleeds (148 [74-300] mcg kg(-1); P = 0.07). Initial and mean dose per day changed as treatment progressed. The DOSE study indicates that frequently bleeding inhibitor patients are prescribed and use higher rFVIIa dosing for all bleed types than recommended in the package insert (90 mcg kg(-1)). The rFVIIa dosing was highly variable within and across bleed types, with higher initial doses used for joint bleeds than muscle and other bleed types, particularly in the first days of treatment. This suggests that patients/caregivers have adopted home treatment strategies based on physician discretion and individual responses and experience.

[A simplified model for kinetics of a tumor cells' population].

A mathematical model of solid tumor growth is suggested. The external influence from the tumor-bearing organism is described separately for cell growth and apoptosis. The model is an ordinary differential equation which provides for use of a variety of dependences for both processes. A solution for a specific example of the processes is obtained in the form of a generalized logistic curve. Our results give clues for such experimental phenomena as spontaneous cessation of cell growth, dependence of life duration on insignificant variations in apoptosis, etc.

Ultra-low-dose estradiol and norethisterone acetate: effective menopausal symptom relief.

OBJECTIVE: To evaluate the efficacy of two ultra-low-dose 17beta-estradiol plus norethisterone acetate (NETA) treatment regimens for relieving menopausal symptoms. DESIGN: A total of 577 postmenopausal women were enrolled, in three treatment groups in a double-blind, randomized, placebo-controlled study of 0.5 mg 17beta-estradiol + 0.1 mg NETA or 0.5 mg 17beta-estradiol + 0.25 mg NETA or placebo. Participants returned at weeks 4, 8, 12 and 24 for climacteric complaint evaluation based on a daily diary vasomotor symptom record. Patients were assessed by the Greene Climacteric Scale and urogenital symptoms were also evaluated. RESULTS: Treatment with ultra-low-dose 0.5 mg 17beta-estradiol + 0.1 mg NETA (0.1 Group) or 0.5 mg 17beta-estradiol + 0.25 mg NETA (0.25 Group) effectively reduced the severity and number of hot flushes within the initial weeks of therapy. Compared to placebo, a rapid, statistically significant decrease in the frequency and severity of hot flushes was achieved by week 3, followed by further improvement which continued throughout the study. There were no statistically significant differences between the active treatment arms. CONCLUSIONS: The data show that both ultra-low-dose regimens are effective in reducing the severity and number of hot flushes compared to placebo, with good safety profiles.

[Kessner index as an exponent of prenatal care]. / Indeks Kessnera--jako wykladnik opieki prenatalnej.

The aim of the study was evaluation of quality of prenatal care by Kessner Index, assessment of the effect intensity of prenatal care on the course of pregnancy and labour, as well as the ultimate delivery effect. The study covered females who gave birth at the Regional Hospital in Bychawa. Data concerning 319 women were analysed. The material obtained was subject to statistical analyses with the use of computer statistical package SPSS/PC 5.01. Prenatal care evaluated by Kessner Index was on the medium level, with the greatest number of pregnant females covered by intermediate care -55.8%. This care was significantly worse among rural females. No significant effect of adequate prenatal care on the ultimate delivery effect was noted, with the best results obtained among females covered with intermediate care.

[A rare case of ovarian leiomyoma. A case report with review of literature]. / Rzadki przypadek miesniaka gladkokomórkowego jajnika.

We report an exceptional case of ovarian leiomyoma in 73 years old patient. Leiomyoma of the ovary is a very rare tumor. Most cases are asymptomatic, this benign neoplasm is usually found incidentally on routine pelvic examination, at surgery or at autopsy. The available literature is reviewed. The possible histogenesis of ovarian leiomyoma was discussed.

[A possible approach to the task of the individual choice of treatment for cancer patients]. / Vozmozhnyi podkhod k zadache individual'nogo vybora lecheniia onkologicheskikh bol'nykh.

A procedure for choosing treatment for a cancer patient is suggested. The method was developed on the basis of data of a retrospective analysis of patient characteristics, type and results of treatment. It suggests the use of a computer and is aimed at assessment of a conventional function of survival for each treatment modality, comparison of these functions and choosing optimal therapeutic regimen with regard to patient characteristics. A method for experimental testing of the above procedure that does not require clinical trials is described.

[Shape of the left ventricular cavity during ejection in patients with ischemic heart disease]. / Forma polosti levogo zheludochka v period izgnaniia u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Different types of left-ventricular wall movement were demonstrated in normal subjects and coronary patients, the differences being due to different degrees of reduction in the equatorial diameter of the cavity in the ejection phase. Rationale are given for using the mean diameter for left-ventricular volume calculations. A linear relationship has been demonstrated between the degree of diameter reduction and the ejection fraction. The latter is shown to be dependent on left-ventricular end diastolic volume. Regional myocardial contractility, a parameter of high diagnostic value, based on segmental ejection fraction, is introduced.