Thomas Hanslik

Acquired hemophilia due to factor VIII inhibitors in 34 patients

BACKGROUND Acquired hemophilia is a rare disease caused by the development of auto-antibodies against factor VIII. SUBJECTS AND METHODS We studied the characteristics and outcomes of 34 patients (19 women and 15 men) with acquired hemophilia from 1980 to 1997. RESULTS The mean age of the patients was 61 years (range, 22-93 years). An underlying disease was observed in 18 (53%) patients: 5 patients had cancer, 4 an autoimmune disorder, 2 a dermatologic disorder, 3 asthma, 3 were postpartum, and 1 had an adverse reaction to ampicillin. Factor VIII level was <5% in 30 (90%) patients; factor VIII antibodies were elevated (>10 Bethesda units) in 23 (69%) patients. Bleeding requiring transfusions was reported in 25 (75%) patients. Human factor VIII was given to 14 patients and porcine factor VIII to 5. Six patients received prothrombin complex concentrates and one desmopressin. Several immunosuppressive treatments were used, mainly corticosteroids, cyclophosphamide, and intravenous immunoglobulin. Bleeding stopped in all but one patient within 2 weeks. Most patients achieved complete remission, although two relapses were observed subsequently. CONCLUSION This large study helps to clarify the presentation and clinical course of acquired hemophilia. Prospective studies are needed to determine the efficacy of treatment.

Varicella in non-immune persons: incidence, hospitalization and mortality rates.

This study was conducted to estimate the varicella morbidity and mortality rates per age group among the non-immune population in France. Morbidity and mortality data for the years 1990-9 were derived from nationwide databases and surveillance systems. An incidence/prevalence model was designed to quantify the non-immune population per age group. The incidence of varicella in the non-immune population peaks during childhood and again in the 25-35 years age group. For children aged 1-4 years, adults aged 25-34 years and those older than 65 years, the hospitalization rates are respectively 235, 1,438 and 8,154 per 100,000 cases, and the death rates are respectively 7, 104 and 5,345 per million cases. Case fatality or case hospitalization rates were not evenly distributed among adults and increased dramatically with age.

Urinary Incontinence in French Women: Prevalence, Risk Factors, and Impact on Quality of Life

BACKGROUND The lack of epidemiologic data on the prevalence of female urinary incontinence (UI) attending general practitioners (GPs) in France led us to conduct a cross-sectional study in our country. OBJECTIVES To determine the prevalence of UI and to assess its impact on the quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study of women aged >18 yr was conducted by attending GPs between June 2007 and July 2007. MEASUREMENTS The main outcome measures were urinary symptoms, functional impairment, International Consultation on Incontinence Questionnaire-Short Form score, and medical care seeking. RESULTS AND LIMITATIONS Overall, 241 GPs enrolled 2183 women seen during 1 d. The prevalence of UI was 26.8% (n=584) and increased with age, body mass index (BMI), and number of children delivered (p<0.0001). Among women with UI, 496 were included in a cross-sectional survey: 45.2% (n=224) had stress UI, 42.1% (n=209) had mixed UI, and 10.9% (n=53) had urge UI, while 2% (n=10) had UI of indeterminate type. Overall, 288 of 496 women (51.8%) stated that UI had a negative impact on their QoL; this effect remained mostly mild or moderate, and only 197 of 496 women (39.7%) had asked for medical help. Longer duration of symptoms, higher frequency of comorbid urinary symptoms, and altered QoL were most frequent among women with mixed UI (p<0.001). Misclassification may have occurred because the diagnosis of UI was based on self-reported data rather than on clinical or urodynamic examinations. CONCLUSIONS UI symptoms were found in almost one in four women attending GPs. Clinical and functional UI impairment were associated with age, BMI, and parity. UI caused distress to women, but only those who were severely affected sought help. The results emphasize the need for policy development for UI prevention and management in France.

Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice.

Summary Despite early diagnosis and treatment with antiviral agents, many herpes zoster patients report persistent pain and marked long‐term reduction in health‐related quality of life. Abstract Understanding the effect of herpes zoster and zoster‐related pain should inform care to improve health‐related quality of life in elderly patients. A 12‐month, longitudinal, prospective, multicenter observational study conducted in primary care in France enrolled patients aged ⩾50 years with acute eruptive herpes zoster. Patient‐reported zoster‐related pain was assessed by validated questionnaires (Douleur Neuropathique en 4 Questions [DN4], Zoster Brief Pain Inventory [ZBPI], and Neuropathic Pain Symptom Inventory [NPSI]) on days 0 and 15, and at months 1, 3, 6, 9, and 12. Health‐related quality of life was assessed by the 12‐item short‐form health survey (SF‐12) and the Hospital Anxiety and Depression scale on day 0 and at months 3, 6, and 12. Of 1358 patients included, 1032 completed follow‐up. Mean ± standard deviation age was 67.7 ± 10.7 (range, 50–95) years; 62.2% were women. Most patients (94.1%) were prescribed antiviral drugs. The prevalence of zoster‐related pain on day 0 and at months 3, 6, 9, and 12 was 79.6%, 11.6%, 8.5%, 7.4%, and 6.0%, respectively. Patients with persistent pain had lower scores on the physical and mental component summaries of the SF‐12 and the ZBPI interference score than those without pain. By logistic regression analysis, main predictive factors on day 0 for postherpetic neuralgia at month 3 were age, male sex, ZBPI interference score, Physical Component Summary score of the SF‐12, and neuropathic quality of pain (DN4 score ⩾4). Despite early diagnosis and treatment with antiviral agents, many patients with herpes zoster experience persistent pain and marked long‐term reduction in health‐related quality of life.

Impact of Chikungunya Virus Infection on Health Status and Quality of Life: A Retrospective Cohort Study

Background Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection. Methodology/Principal Findings In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK–) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK– of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6–2.2), myalgia (1.9; 1.5–2.3), fatigue (2.3; 1.8–3), depression (2.5; 1.5–4.1) and hair loss (3.8; 1.9–7.6). There was no significant difference between CHIK+ and CHIK– subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK– (p = 0.04). There was no significant difference between the two groups for the Mental Component Summary. Conclusions/Significance More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK–. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate.

The Chikungunya Epidemic on La Réunion Island in 2005–2006: A Cost-of-Illness Study

Background This study was conducted to assess the impact of chikungunya on health costs during the epidemic that occurred on La Réunion in 2005–2006. Methodology/Principal Findings From data collected from health agencies, the additional costs incurred by chikungunya in terms of consultations, drug consumption and absence from work were determined by a comparison with the expected costs outside the epidemic period. The cost of hospitalization was estimated from data provided by the national hospitalization database for short-term care by considering all hospital stays in which the ICD-10 code A92.0 appeared. A cost-of-illness study was conducted from the perspective of the third-party payer. Direct medical costs per outpatient and inpatient case were evaluated. The costs were estimated in Euros at 2006 values. Additional reimbursements for consultations with general practitioners and drugs were estimated as €12.4 million (range: €7.7 million–€17.1 million) and €5 million (€1.9 million–€8.1 million), respectively, while the cost of hospitalization for chikungunya was estimated to be €8.5 million (€5.8 million–€8.7 million). Productivity costs were estimated as €17.4 million (€6 million–€28.9 million). The medical cost of the chikungunya epidemic was estimated as €43.9 million, 60% due to direct medical costs and 40% to indirect costs (€26.5 million and €17.4 million, respectively). The direct medical cost was assessed as €90 for each outpatient and €2,000 for each inpatient. Conclusions/Significance The medical management of chikungunya during the epidemic on La Réunion Island was associated with an important economic burden. The estimated cost of the reported disease can be used to evaluate the cost/efficacy and cost/benefit ratios for prevention and control programmes of emerging arboviruses.

Autoimmune diseases in HIV-infected patients: 52 cases and literature review

OBJECTIVES 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.

Lyme disease in France: a primary care-based prospective study

To estimate the incidence of Lyme borreliosis in France, describe its clinical presentations, and assess its potential risk factors, we conducted a nationwide prospective study in the French Sentinelles Network, consisting of 1178 general practitioners (GPs). Of these, 875 (74%), i.e. 1.6% of all French GPs, participated in the study from May 1999 to April 2000. Eighty-six cases of Lyme disease were reported and validated, of which 77 (90%) consisted of erythema migrans. At national level, the incidence was estimated at 9.4/100,000 inhabitants. Compared to the French general population, Lyme disease patients were older (P<10(-4)), more were living in rural areas (P<10(-3)), and amongst the working population, more were farmers (P<10(-3)) and fewer, salaried workers (P<0.005). Cervidae density correlated strongly with the estimated regional incidence of Lyme disease (r=0.82). Both incidence data and identified risk factors can help to target measures for its prevention and treatment.

The use of vitamin K in patients on anticoagulant therapy: a practical guide.

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication.The risk of bleeding increases dramatically when the INR exceeds 4.0–6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage.As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1–2.5mg of oral phytomenadione (vitamin K1), reduces the range of INR from 5.0–9.0 to 2.0–5.0 within 24–48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.

Prévalence et prise en charge de l'insuffisance cardiaque en France : enquête nationale auprès des médecins généralistes du réseau Sentinelles

BACKGROUND Epidemiological data on heart failures epidemiology in France are scarce and mostly hospital based. The present studys objective is to estimate the prevalence of heart failure (HF) and its management, in subjects aged 60 years and older seen by the French general practitioners (GP). METHODS A standardised questionnaire was mailed to 900 GPs of the Sentinelles network, requiring answers for any patient aged 60 years and more, seen on a randomly assigned single day of year 2002. National census and health insurance data were used to estimate prevalence. RESULTS 434 GPs answered, reporting data for 1797 patients aged 60 years and more. The 214 patients with HF, aged 79 years on average, had been seen by a cardiologist in 95% of cases. Results of an echocardiography was available for 58% of HF patients. Compared to non-HF patients, patients with HF were significantly more dependent, more frequently requiring home visit of the GP and more frequently hospitalised (p < 0.001, age adjusted). All the 42% HF patients with a reported left ventricle ejection fraction lower than 40% were treated with an angiotensin converting enzyme inhibitor or an angiotensin receptor inhibitor. The prevalence of HF among patients aged 60 years and older was estimated at 11.9% in general practice (95% confidence interval: 10.5-13.5), and at 2.19% (1.9-2.5) in the general population. The prevalence increased with age, over 20% in persons aged 80 years and more. CONCLUSION HF in patients aged 60 years and more seen in general practice in France is characterised by a high prevalence and medical consumption in terms of required number of hospitalisation and GPs home visit. For the GP, the diagnosis of HF relies on the cardiologist more than on an echocardiography. The therapeutic management seems to fit the actual recommendations.