Impact of the Use of a Rapid Diagnostic Test for Visceral Leishmaniasis on Clinical Practice in Ethiopia: A Retrospective Study

Background

Diagnostic guidelines for Visceral Leishmaniasis (VL) in the East African region are complex. Patients meeting the VL clinical case definition should be tested by rK39 rapid diagnostic test (RDT) followed by the Direct Agglutination Test (DAT) or tissue aspiration if RDT-negative. Otherwise, RDT-positive patients should be started on VL treatment. We evaluated how this guideline is adhered to by assessing the routine clinical practice in a university hospital in North-West Ethiopia.

Methods

Retrospective record analysis was done for all patients who had an rK39-RDT done at University of Gondar (UoG) Hospital between June 2012 and June 2013. We described the diagnostic work-up performed and the proportion initiated on VL treatment by test result.

Results/Findings

From a total of 928 patients tested, 308 (33.2%) were rK39 RDT-positive. Spleen or bone marrow aspiration was done for 237 (77.2%) RDT-positive patients. Of these, 165 were confirmed parasitologically, yielding a positive predictive value of 69.6%. Only 126 (20.3%) of the 620 patients with a negative rK39 test underwent further testing by tissue aspiration, of which 22 (17.5%) were also parasitology positive. HIV test results were available for 570 (61.4%) patients and 36 (6.3%) were HIV-infected. Of the 187 parasitologically confirmed patients, 182 (97.3%) were started on VL treatment.

Conclusions / Discussion

A negative rK39 test was often not followed by further testing and a positive rK39 test result was followed by tissue aspiration in three out of four cases. Further research is required to understand why the diagnostic work-up did not comply with the guidelines, including evaluating adherence to the VL clinical case definition and quality of rK39-RDT testing.     

Immunologic dysfunction in patients with classic hemophilia receiving lyophilized factor VIII concentrates and cryoprecipitate.

The occurrence of the acquired immune deficiency syndrome (AIDS) in patients with hemophilia has suggested that an infectious agent transmitted through the frequent use of pooled blood products could be responsible. To determine if the amount or type of factor VIII preparation alters the risk of acquiring immune defects, three groups of asymptomatic heterosexual men were studied: 34 with severe classic hemophilia who were receiving lyophilized factor VIII concentrate, 10 with either mild classic hemophilia or moderately severe von Willebrand''s disease who were receiving cryoprecipitate and 22 normal men who served as controls. Anergy was noted in 68%, 57% and 5% respectively of the three groups. In comparison with the control group, the group treated with lyophilized factor VIII concentrate had a significantly decreased mean ratio of helper to suppressor T lymphocytes, poor responses of the lymphocytes to mitogens, high unstimulated background activity of these cells and significantly elevated serum IgG levels. Although some of the patients with classic hemophilia who were treated with cryoprecipitate were also anergic, they did not manifest these in-vitro abnormalities. The data indicate that a majority of apparently immunocompetent individuals with classic hemophilia show in-vivo and in-vitro evidence of impaired cellular immunity and may be at risk for the development of opportunistic infections and neoplasms.     

Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment.

OBJECTIVES--To assess women''s preferences for, and the acceptability of, medical abortion and vacuum aspiration in the early first trimester. DESIGN--Patient centred, partially randomised trial. Medical abortion was performed with mifepristone 600 mg followed 48 hours later by gemeprost 1 mg vaginal pessary. Vacuum aspiration was performed under general anaesthesia. SETTING--Teaching hospital in Scotland. PATIENTS--363 women undergoing legal induced abortion at less than nine weeks'' gestation. MAIN OUTCOME MEASURES--Women''s preferences for method of abortion before abortion; acceptability judged two weeks after abortion by recording the method women would opt to undergo in future and by semantic differential rating technique. RESULTS--73 (20%) women preferred to undergo medical abortion, and 95 (26%) vacuum aspiration; 195 (54%) were willing to undergo either method, and were allocated at random. Both procedures were highly acceptable to women with preferences. Gestation had a definite effect on acceptability in randomised women; at less than 50 days there were no differences, but between 50 and 63 days vacuum aspiration was significantly more acceptable. CONCLUSIONS--Women who wish to use a particular method should be allowed their choice, regardless of gestation. Women of 50-63 days'' gestation without preferences for a particular method are likely to find vacuum aspiration more acceptable. A patient centred, partially randomised trial design may be a useful tool in pragmatic research.     

Intranasal desmopressin (DDAVP) by spray in mild hemophilia A and von Willebrand's disease type I

Desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP) has mostly been given by the parenteral route for the treatment of mild hemophilia A and von Willebrand's disease type I. In the present study the hemostatic effects of desmopressin acetate administered intranasally by spray in a dose of 300 micrograms and intravenously 0.3-0.4 micrograms/kg were assessed and compared in 8 patients with hemophilia A and 22 patients with von Willebrand's disease type I. A bioequivalent response to intravenous and intranasal desmopressin acetate was found in Factor VIII coagulant activity (VIII:C) in the hemophilia patients. In the von Willebrand patients, an equivalent shortening of the bleeding time was seen after the two modes of administration, even though intravenous injection gave a higher increase in plasma levels of VIII:C and vWF:Ag. In five patients with von Willebrand's disease the duration of the spray effect on VIII:C and vWF:Ag was followed for 24 h. After 12 h the mean level of VIII:C was 1.4, and of vWF:Ag 1.5, times the basal level. The findings suggest that the spray can be recommended for home or prophylactic treatment of patients with mild hemophilia A and von Willebrand's disease.     

西安地区儿童支气管哮喘吸入性过敏原的调查分析

目的:探讨西安地区儿童支气管哮喘吸入性过敏原的分布情况。方法:选择950例来自西安地区的支气管哮喘患儿为研究对象,采用过敏原皮肤点刺试验检测,以组胺作为阳性对照,生理盐水为阴性对照,分析不同年龄和性别的患儿过敏原的分布情况。结果:950例支气管哮喘患儿中,384例皮肤点刺过敏原检测呈阳性,占40.4%,男女患儿过敏原检测阳性分布无明显差异(P0.05);尘螨为主要的过敏原,其次为艾蒿和霉菌类;随着患儿年龄的增加,其过敏原检测的阳性率明显升高(P0.05),且大多数过敏原检测阳性患儿至少合并2-3种过敏原阳性。结论:西安地区支气管哮喘患儿吸入性过敏原阳性率与其性别无关,但与其年龄有关,过敏原以尘螨类为主,大多数检测阳性的患儿对至少一种以上的过敏原阳性。     

Cumulative radiation dose estimates from medical imaging in paediatric patients with non-oncologic chronic illnesses. A systematic review

Paediatric patients with non-oncologic chronic illnesses often require ongoing care that may result in repeated imaging and exposure to ionizing radiation from both diagnostic and interventional procedures. In this study the scientific literature on cumulative effective dose (CED) of radiation accrued from medical imaging among specific cohorts of paediatric, non-oncologic chronic patients (inflammatory bowel disease, cystic fibrosis, congenital heart disease, shunt-treated hydrocephalus, hemophilia, spinal dysraphism) was systematically reviewed.We conducted PubMed/Medline, Scopus and EMBASE searches of peer-reviewed papers on CED from diagnostic and therapeutic radiological examinations. No time restriction was introduced in the search. Only studies reporting CEDs accrued for a period >1 year were included.We found that the annual CED was relatively low (<3 mSv/year) in cystic fibrosis, congenital heart disease, patients with cerebrospinal fluid shunts and hemophilia, while being moderate (>3–20 mSv/year) in Crohn's patients.This extra yearly radiation exposure accrues over the lifetime and can reach high values (>100 mSv) in selected cohorts of paediatric chronic patients.     

Factor VIII hydrolysis mediated by anti-factor VIII autoantibodies in acquired hemophilia

Acquired hemophilia is a rare hemorrhagic disorder caused by the spontaneous appearance of inhibitory autoantibodies directed against endogenous coagulation factor VIII (FVIII). Inhibitory Abs also arise in patients with congenital hemophilia A as alloantibodies directed to therapeutic FVIII. Both autoimmune and alloimmune inhibitors neutralize FVIII by steric hindrance. We have described FVIII-hydrolyzing IgG in 50% of inhibitor-positive patients with severe hemophilia A that inactivate therapeutic FVIII. In this study, we investigated the presence of autoimmune FVIII-hydrolyzing IgG in patients with acquired hemophilia. Pooled IgG from healthy donors demonstrated moderate FVIII-hydrolyzing activity (56 +/- 26 micromol/min/mol). Purified IgG from 21 of 45 patients with acquired hemophilia demonstrated FVIII hydrolysis rates (mean 219 +/- 94 micromol/min/mol) significantly greater than that of control IgG. Three of four patients followed over the course of the disease had rates of FVIII hydrolysis that co-evolved with inhibitory titers in plasma, suggesting that IgG-mediated FVIII hydrolysis participates, in part, in FVIII inactivation. The present work extends the scope of the diseases associated with FVIII proteolysis and points toward the importance of FVIII as a key target substrate for hydrolytic immunoglobulins. Our data suggest that elevated levels of FVIII-hydrolyzing IgG in acquired hemophilia result from the exacerbation of a physiological catalytic immune response.     

心理咨询对血友病患者心境障碍的干预效果

目的:观察心理咨询对血友病心境障碍患者的干预效果。方法:选择2014年1月~2015年4月在哈尔滨医科大学附属第四医院血液内科接受治疗的血友病患者63例,年龄从18~55岁且具有良好的思维能力和判断能力,并获得知情同意的,用心理咨询的方法前后用汉密尔顿焦虑量表和汉密尔顿抑郁量表进行测查,得出结论。结果:在对63例血友病的患者心理咨询及测查的结果看,血友病患者中有抑郁情绪的比率从88.9%降低到63.5%,抑郁情绪的平均值从17.62降到9.98差异显著。有焦虑情绪的比率从77.8%降低到57.1%,平均值从20.87降到12.06差异显著。具有统计学意义,这充分说明了心理咨询对血友病患者是有效果的。结论:用心理咨询的方法对血友病患者进行心理干预是有效的。     

Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia

Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies to endogenous FVIII in individuals with acquired hemophilia. We have described FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in acquired hemophilia patients. Here, we compared the properties of proteolytic auto- and allo-antibodies. Rates of FVIII hydrolysis differed significantly between the two groups of antibodies. Proline-phenylalanine-arginine-methylcoumarinamide was a surrogate substrate for FVIII-hydrolyzing autoantibodies. Our data suggest that populations of proteolytic anti-FVIII IgG in acquired hemophilia patients are different from that of inhibitor-positive hemophilia A patients.     

Development and Characterization of Recombinant Ovine Coagulation Factor VIII

Animal models of the bleeding disorder, hemophilia A, have been an integral component of the biopharmaceutical development process and have facilitated the development of recombinant coagulation factor VIII (fVIII) products capable of restoring median survival of persons with hemophilia A to that of the general population. However, there remain several limitations to recombinant fVIII as a biotherapeutic, including invasiveness of intravenous infusion, short half-life, immunogenicity, and lack of availability to the majority of the world''s population. The recently described ovine model of hemophilia A is the largest and most accurate phenocopy. Affected sheep die prematurely due to bleeding-related pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII. Herein, we describe the development and characterization of recombinant ovine fVIII (ofVIII) to support further the utility of the ovine hemophilia A model. Full-length and B-domain deleted (BDD) ofVIII cDNAs were generated and demonstrated to facilitate greater biosynthetic rates than their human fVIII counterparts while both BDD constructs showed greater expression rates than the same-species full-length versions. A top recombinant BDD ofVIII producing baby hamster kidney clone was identified and used to biosynthesize raw material for purification and biochemical characterization. Highly purified recombinant BDD ofVIII preparations possess a specific activity nearly 2-fold higher than recombinant BDD human fVIII and display a differential glycosylation pattern. However, binding to the carrier protein, von Willebrand factor, which is critical for stability of fVIII in circulation, is indistinguishable. Decay of thrombin-activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic stability. Furthermore, intravenous administration of ofVIII effectively reverses the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII should facilitate the maintenance of the ovine hemophilia A herd and their utilization as a relevant large animal model for the research and development of novel nucleic acid and protein-based therapies for hemophilia A.     

Aspiration-Related Deaths in 57 Consecutive Patients: Autopsy Study

Background

Aspiration can cause a diverse spectrum of pulmonary disorders some of which can lead to death but can be difficult to diagnose.

Patients and Methods

The medical records and autopsy findings of 57 consecutive patients in whom aspiration was the immediate cause of death at Mayo Clinic (Rochester, MN, USA) over a 9-yr period, from January 1 2004 to December 31 2012 were analyzed.

Results

The median age at death was 72 years (range, 13–95 years) and included 39 (68%) males. The most common symptom before death was dyspnea (63%) and chest radiography revealed bilateral infiltrates in the majority (81%). Most common precipitating factors for aspiration were depressed consciousness (46%) and dysphagia (44%). Aspiration-related syndromes leading to death were aspiration pneumonia in 26 (46%), aspiration pneumonitis in 25 (44%), and large airway obstruction in 6 patients (11%). Aspiration was clinically unsuspected in 19 (33%) patients. Antimicrobial therapy had been empirically administered to most patients (90%) with aspiration pneumonia and aspiration pneumonitis.

Conclusion

We conclude aspiration-related deaths occur most commonly in the elderly with identifiable risks and presenting bilateral pulmonary infiltrates. One-third of these aspiration-related pulmonary syndromes were clinically unsuspected at the time of death.     

Immunologic studies in asymptomatic hemophiliac patients

Various immunological parameters were studied in 20 asymptomatic patients with hemophilia A, 3 patients with hemophilia B and 1 patient with von Willebrand disease. Patients were treated with cryoprecipitate or fresh frozen plasma. Significantly decreased mean percentage and absolute count (p less than 0.01) of peripheral blood E-rosette-forming cells compared to controls was found. There were normal mean percentages and absolute counts of lymphocytes, T-helper inducer, T-suppressor cytotoxic and natural killer cells. The proportion and absolute number of B cells was slightly increased. Significantly decreased natural killer cell activity (p = 0.02) of peripheral blood lymphocytes was observed. Our results indicate that asymptomatic patients with hemophilia may have early evidence of immunodeficiency.     

Acid-fast bacilli in fine needle aspiration smears from tuberculous lymph nodes. Where to look for them

OBJECTIVE: To analyze where acid-fast bacilli (AFB) are most often seen in smears prepared from tuberculous lymph nodes. STUDY DESIGN: Patients referred for fine needle aspiration cytology for evaluation of lymphadenopathy between March 1994 and June 1998 were analyzed. Only those cases clinically and therapeutically proven to be tuberculous were included in the study. RESULTS: Of 783 cases analyzed, 213 (27.2%) were tuberculous. Aspirates obtained were of three types: blood-mixed particles, caseous material and pus. Five cytologic pictures were seen: epithelioid cell granulomas alone or with coexistent necrosis, AFB or both, and necrosis with AFB. AFB were most often seen in purulent aspirates, followed by caseous and least often in blood-mixed particles. Granulomas were most often seen when the aspirate was blood-mixed particles, followed by caseous and, least often, pus. CONCLUSION: AFB detection should be carried out on all suspected tuberculous patients. The relationship between the presence of granuloma and of AFB is inverse. The chance of finding AFB is highest in patients presenting with a cold abscess and yielding pus on aspiration followed by patients who yield caseous material on aspiration.     

The Isaacs Endometrial Cell Sampler. An evaluation in 100 patients with postmenopausal bleeding

The Curity Isaacs Endometrial Cell Sampler was used to obtain cytologic material from 100 consecutive patients presenting with postmenopausal bleeding. It was followed by uterine curettage to obtain material for histology. Satisfactory endometrial aspiration smears were obtained from 92 patients, whereas curettage yielded endometrial tissue in only 48. Of 17 patients with histologic confirmation of malignancy, 7 had smears diagnosed as showing malignancy, and 7 had smears showing hyperplastic changes; 3 of the aspiration smears were judged to be unsatisfactory for cytologic evaluation. All the carcinomas were found in the hyperplastic, malignant or unsatisfactory smears. This technique is worthy of further study.     

Prevalence of human immunodeficiency virus (HIV) infection among hemophiliacs in Fukuoka, Japan

To determine when the hemophiliacs in Fukuoka prefecture, Japan, first became positive for antibodies, we tested human immunodeficiency virus (HIV) antibodies on serum samples obtained from 1976-1987 stored at -30 C. Fifteen out of 64 hemophilia A patients (23.4%), five out of 11 hemophilia B patients (45.5%), but none of 17 patients with von Willebrand's disease (0%) were positive for HIV antibodies. In this series, two with hemophilia A became positive for HIV antibodies for the first time in 1983, and in 1984 another four with hemophilia A and one with hemophilia B became positive.     

参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床研究

目的:探究参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床疗效。方法:选择2012年6月~2015年6月期间,我院收治急性酒精中毒合并吸入性肺炎患者112例为研究对象,采用随机数字法将其随机分为观察组(57例)和对照组(55例)。对照组在基础治疗的基础上给予布地奈德治疗,观察组在对照组的基础上联合参麦注射液治疗,收集并分析治疗后两组患者症状恢复时间、症状消失时间、清醒后不良反应发生情况、治疗前后肝功能指标及血清炎性因子指标。结果:观察组患者清醒时间、血压恢复时间及头晕、头痛、电解质紊乱的发生率均显著低于对照组(P0.05);治疗后两组患者间天冬氨酸氨基转移酶(AST)、丙氨酸转氨酶(ALT)、γ-谷氨酰基转移酶(GGT)水平均出现显著降低,且观察组均显著低于对照组(P0.05);观察患者咳嗽消失、气喘缓解、哮鸣音消失及湿罗音消失时间均显著低于对照组(P0.05);治疗后两组患者血清IL-6、TNF-α及CRP水平均显著降低,且观察组均显著低于对照组(P0.05)。结论:参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎疗效可靠,能够有效缩短患者酒精中毒症状的恢复与消失时间,降低清醒后不良症状的发生率,并且能改善患者肝功能、减轻炎症反应,具有重要的临床价值。     

Computed tomography-guided fine needle aspiration of peripheral lung opacities. An initial diagnostic procedure?

OBJECTIVE: To evaluate the results of computed tomography (CT)-guided fine needle aspiration (FNA) cytology following negative fiberoptic bronchoscopy and sputum cytology. STUDY DESIGN: Retrospective study of 64 patients who underwent CT-guided needle aspiration of lung opacities over one year. Following a review of the CT studies, patients were selected according to image characteristics of a primary neoplasm and pleural effusion in cases with pleural lesions. The lesions were classified into three categories--intrapulmonary and peripheral pulmonary, pleuropulmonary and pleural--and were localized and aspirated under CT using a fine needle (22-23 gauge) for obtaining cellular material. Lesions diagnosed as benign on FNA cytology were followed by serial CT scans for a period of two years at six-month intervals. RESULTS: Thirty-nine of 64 (61%) lesions were diagnosed as malignant on FNA cytology and 25 of 64 (39%) as benign. There was one false negative case. There were no serious complications from the procedure. CONCLUSION: FNA under CT guidance may be applied as the initial procedure in the diagnosis of peripheral malignant pulmonary lesions, rendering a high diagnostic yield.     

Pulmonary Aspiration after Fibre-endoscopy of the Upper Gastrointestinal Tract

Pulmonary aspiration occurred in 16 out of 65 patients (24·6%) undergoing fibre-endoscopic examinations of the upper gastrointestinal tract under intravenous sedation, but it was rarely followed by serious complications. Aspiration was found to occur under sedation with diazepam alone, diazepam with atropine, and with chlormethiazole. The most important factors contributing to aspiration are the local pharyngeal anaesthesia and the mechanical interference of the fibrescope with laryngeal closure and swallowing. The patient is also at risk of aspiration after completion of the procedure and should remain recumbent until the local anaesthesia has worn off.     

Gene therapy on demand: Site specific regulation of gene therapy

Since 1990 when the first clinical gene therapy trial was conducted, much attention and considerable promise have been given to this form of treatment. Gene therapy has been used with success in patients suffering from severe combined immunodeficiency syndromes (X-SCID and ADA-deficiency), Leber's congenital amaurosis, hemophilia, β-thalassemia and adrenoleukodystrophy. Last year, the first therapeutic vector (Glybera) for treatment of lipoprotein lipase deficiency has been registered in the European Union. Nevertheless, there are still several numerous issues that need to be improved to make this technique more safe, effective and easily accessible for patients.