scholarly journals Benznidazole-Related Adverse Drug Reactions and Their Relationship to Serum Drug Concentrations in Patients with Chronic Chagas Disease

2012 ◽  
Vol 57 (1) ◽  
pp. 390-395 ◽  
Author(s):  
María-Jesús Pinazo ◽  
Laura Guerrero ◽  
Elizabeth Posada ◽  
Elena Rodríguez ◽  
Dolors Soy ◽  
...  

ABSTRACTFor treating Chagas disease (CD), a current worldwide health problem, only benznidazole and nifurtimox have been approved to be used. In both cases, unwanted drug-related adverse events (ADRs) are frequent when these drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole ADRs and their relationship to serum concentrations in patients with chronicTrypanosoma cruziinfection in order to perform more accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12 months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow-up, and the overall average ADR incidence was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, 7 among them due to severe adverse effects. The mean duration of treatment before withdrawal was 11 days. Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60 of follow-up and evaluated according to clinical and epidemiological variables and ADR severity. No relationship was found between the benznidazole serum concentration and the ADRs. The mean (standard deviation) trough serum benznidazole concentrations (all below 20 mcg/ml) on days 15, 30, 45, and 60 were 6.4 (1.9), 6.1 (1.8), 6.2 (2.2), and 5.7 (1.7) μg/ml, respectively. Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further, well-controlled studies are necessary to establish the optimal regimen for benznidazole in adults with chronic CD.

2013 ◽  
Vol 57 (9) ◽  
pp. 4518-4523 ◽  
Author(s):  
Catalina Muñoz ◽  
Inés Zulantay ◽  
Werner Apt ◽  
Sylvia Ortiz ◽  
Alejandro G. Schijman ◽  
...  

ABSTRACTCurrently, evaluation of drug efficacy for Chagas disease remains a controversial issue with no consensus. In this work, we evaluated the parasitological efficacy of Nifurtimox treatment in 21 women with chronic Chagas disease from an area of endemicity in Chile who were treated according to current protocols. Under pre- and posttherapy conditions, blood (B) samples and xenodiagnosis (XD) samples from these patients were subjected to analysis by real-time PCR targeting the nuclear satellite DNA ofTrypanosoma cruzi(Sat DNA PCR-B, Sat DNA PCR-XD) and by PCR targeting the minicircle of kinetoplast DNA ofT. cruzi(kDNA PCR-B, kDNA PCR-XD) and byT. cruzigenotyping using hybridization minicircle tests in blood and fecal samples ofTriatoma infestansfeed by XD. In pretherapy, kDNA PCR-B and kDNA PCR-XD detectedT. cruziin 12 (57%) and 18 (86%) cases, respectively, whereas Sat DNA quantitative PCR-B (qPCR-B) and Sat DNA qPCR-XD were positive in 18 cases (86%) each. RegardingT. cruzigenotype analysis, it was possible to observe in pretherapy the combination of TcI, TcII, and TcV lineages, including mixtures ofT. cruzistrains in most of the cases. At 13 months posttherapy,T. cruziDNA was detectable in 6 cases (29.6%) and 4 cases (19.1%) by means of Sat DNA PCR-XD and kDNA PCR-XD, respectively, indicating treatment failure with recovery of live parasites refractory to chemotherapy. In 3 cases, it was possible to identify persistence of the baseline genotypes. The remaining 15 baseline PCR-positive cases gave negative results by all molecular and parasitological methods at 13 months posttreatment, suggesting parasite response. Within this follow-up period, kDNA PCR-XD and Sat DNA qPCR-XD proved to be more sensitive tools for the parasitological evaluation of the efficacy of Nifurtimox treatment than the corresponding PCR methods performed directly from blood samples.


1993 ◽  
Vol 18 (1) ◽  
pp. 115-118 ◽  
Author(s):  
J. STEVENSON ◽  
I. W. R. ANDERSON

160 consecutive hand infections presented to an Accident and Emergency department over a four-month period. All but one were treated solely on an out-patient basis. The mean delay to presentation was three days, the mean duration of treatment was six days. Follow-up to complete resolution was achieved in 89% of cases. No patients were treated with parenteral antibiotics. The need for careful assessment, early aggressive surgery, and meticulous attention to the principles of wound care by experienced clinicians is emphasized.


2017 ◽  
Vol 24 (6) ◽  
pp. 805-810 ◽  
Author(s):  
Zoé LE van Kempen ◽  
Cyra E Leurs ◽  
Birgit I Witte ◽  
Annick de Vries ◽  
Mike P Wattjes ◽  
...  

Background: Natalizumab is efficacious in the treatment of relapsing-remitting multiple sclerosis. All patients receive the same treatment regimen of 300 mg every 4 weeks, despite differences in pharmacokinetics between individual patients. Objective: To give neurologists insight into natalizumab concentrations at time of re-dosing, we investigated longitudinal natalizumab concentrations in 80 patients in relation to disease activity, with possible influencing factors. Methods: In a prospective observational cohort study, natalizumab trough serum concentrations were measured in 80 patients. Data on demographics, duration of treatment, Expanded Disability Status Scale, clinical exacerbations, brain magnetic resonance imaging (MRI), and body weight were collected. Results: We measured high (≥10 µg/mL) natalizumab trough concentrations in 94% of patients. Intra-individual concentrations were stable. The spread in concentrations was substantial and did not correlate with disease activity. We found a negative association between natalizumab concentration and body weight (β = −0.30, p = 0.010). Interpretation: The majority of patients showed high natalizumab serum concentrations at time of re-dosing. Alternative treatment regimens could lead to more efficient use of natalizumab, but caution is warranted regarding the possibility of recurrence of disease activity. Prospective clinical trials are needed to establish the safety of extended dose intervals in natalizumab treatment.


2016 ◽  
Vol 54 (6) ◽  
pp. 1566-1572 ◽  
Author(s):  
Alba Abras ◽  
Montserrat Gállego ◽  
Teresa Llovet ◽  
Silvia Tebar ◽  
Mercedes Herrero ◽  
...  

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity withLeishmaniaspp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity withLeishmaniaspecies. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.


2001 ◽  
Vol 94 (5) ◽  
pp. 757-764 ◽  
Author(s):  
José Guimarães-Ferreira ◽  
Fredrik Gewalli ◽  
Pelle Sahlin ◽  
Hans Friede ◽  
Py Owman-Moll ◽  
...  

Object. Brachycephaly is a characteristic feature of Apert syndrome. Traditional techniques of cranioplasty often fail to produce an acceptable morphological outcome in patients with this condition. In 1996 a new surgical procedure called “dynamic cranioplasty for brachycephaly” (DCB) was reported. The purpose of the present study was to analyze perioperative data and morphological long-term results in patients with the cranial vault deformity of Apert syndrome who were treated with DCB. Methods. Twelve patients have undergone surgery performed using this technique since its introduction in 1991 (mean duration of follow-up review 60.2 months). Eleven patients had bicoronal synostosis and one had a combined bicoronal—bilambdoid synostosis. Perioperative data and long-term evolution of skull shape visualized on serial cephalometric radiographs were analyzed and compared with normative data. Changes in mean skull proportions were evaluated using a two-tailed paired-samples t-test, with differences being considered significant for probability values less than 0.01. The mean operative blood transfusion was 136% of estimated red cell mass (ERCM) and the mean postoperative transfusion was 48% of ERCM. The mean operative time was 218 minutes. The duration of stay in the intensive care unit averaged 1.7 days and the mean hospital stay was 11.8 days. There were no incidences of mortality and few complications. An improvement in skull shape was achieved in all cases, with a change in the mean cephalic index from a preoperative value of 90 to a postoperative value of 78 (p = 0.000254). Conclusions. Dynamic cranioplasty for brachycephaly is a safe procedure, yielding high-quality morphological results in the treatment of brachycephaly in patients with Apert syndrome.


1993 ◽  
Vol 79 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Robert F. Spetzler ◽  
James M. Herman ◽  
Stephen Beals ◽  
Edward Joganic ◽  
John Milligan

✓ Through the combined efforts of neurosurgeons, head and neck surgeons, and craniofacial surgeons, the standard transbasal approach to the frontal fossa has been modified to include removal of the orbital roofs, nasion, and ethmoid sinuses. This approach has been combined further with facial disassembly procedures to provide extensive midline exposure to the midface and clival region. Extended frontal approaches, however, necessitate removal of the crista galli and sectioning of the olfactory rootlets with the associated risk of anosmia, cerebrospinal fluid (CSF) leak, and the need for complex reconstruction of the frontal floor. To avoid these problems, the authors have modified the technique of handling the cribriform plate to preserve the olfactory unit. Circumferential osteotomy cuts are made around the cribriform plate to allow an en bloc removal with its attachment to both the dura and underlying mucosa. Opening of the dura is avoided and the cribriform bone is used to reconstruct the floor. Four patients underwent this approach, for treatment of an angiofibroma in three and a fibrosarcoma in one. The mean follow-up period was 7 months. No patients developed a CSF leak, and within 8 weeks olfaction had returned in all patients. There was no other associated morbidity. These data suggest that this modification of the transbasilar approach can alleviate extensive reconstructive procedures and CSF leaks while preserving olfaction.


2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 81-86 ◽  
Author(s):  
Kang-Du Liu ◽  
Wen-Yuh Chung ◽  
Hsiu-Mei Wu ◽  
Cheng-Ying Shiau ◽  
Ling-Wei Wang ◽  
...  

Object. The authors sought to determine the value of gamma knife surgery (GKS) in the treatment of cavernous hemangiomas (CHs). Methods. Between 1993 and 2002, a total of 125 patients with symptomatic CHs were treated with GKS. Ninety-seven patients presented with bleeding and 45 of these had at least two bleeding episodes. Thirteen patients presented with seizures combined with hemorrhage, and 15 patients presented with seizures alone. The mean margin dose of radiation was 12.1 Gy and the mean follow-up time was 5.4 years. In the 112 patients who had bled the number of rebleeds after GKS was 32. These rebleeds were defined both clinically and based on magnetic resonance imaging for an annual rebleeding rate of 32 episodes/492 patient-years or 6.5%. Twenty-three of the 32 rebleeding episodes occurred within 2 years after GKS. Nine episodes occurred after 2 years; thus, the annual rebleeding rate after GKS was 10.3% for the first 2 years and 3.3% thereafter (p = 0.0038). In the 45 patients with at least two bleeding episodes before GKS, the rebleeding rate dropped from 29.2% (55 episodes/188 patient-years) before treatment to 5% (10 episodes/197 patient-years) after treatment (p < 0.0001). Among the 28 patients who presented with seizures, 15 (53%) had good outcomes (Engel Grades I and II). In this study of 125 patients, symptomatic radiation-induced complications developed in only three patients. Conclusions. Gamma knife surgery can effectively reduce the rebleeding rate after the first symptomatic hemorrhage in patients with CH. In addition, GKS may be useful in reducing the severity of seizures in patients with CH.


2021 ◽  
pp. 112067212110483
Author(s):  
Selma Özbek-Uzman ◽  
Züleyha Yalnız-Akkaya ◽  
Evin Şingar Özdemir ◽  
Ayşe Burcu

Purpose: We aimed to investigate the efficacy and safety of single-dose autologous serum eye drops (ASEDs) for treatment of persistent corneal epithelial defects (PEDs). Methods: About 34 eyes of 26 patients treated from March 2016 to May 2020 with a single dose of ASEDs for PEDs that did not respond to conventional treatment were retrospectively evaluated. Patient demographics, predisposing factors, size, and duration of the PED, duration of treatment, and dosage of ASEDs, PED healing time, success rate of the ASED treatment, and follow-up time after the onset of ASED treatment were recorded. Autologous serum eye drops (20%) were prepared by diluting the serum with preservative-free artificial tears in single-dose vials. Vials were stored at −20°C and used daily after dissolving. Results: The mean patient age was 47.0 ± 18.5 years, and 13 (50%) of the patients were male. The most common indication for ASEDs was PED after keratoplasty. The mean duration of ASED treatment was 8.5 ± 6.3 months, and mean follow-up time was 22.8 ± 12.2 months. Autologous serum eye drop treatment was effective in 25 (73.5%) eyes and partially effective in 5 (14.7%) eyes. None of the eyes displayed complications related to the treatment. Conclusion: In patients with PED for whom conservative treatment is insufficient, ASEDs prepared by dilution with preservative-free artificial tears in single-dose vials and administered based on the daily use principle appear to be effective and safe.


2005 ◽  
Vol 102 ◽  
pp. 225-229 ◽  
Author(s):  
En-Min Wang ◽  
Li Pan ◽  
Bing-Jiang Wang ◽  
Nan Zhang ◽  
Liang-Fu Zhou ◽  
...  

Object. The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. Methods. Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel—Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5–55 mm). The mean follow up after GKS was 66 months (range 24–114 months). The mean prescription dose was 17.2 Gy (range 12–24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. Conclusions. Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.


2003 ◽  
Vol 99 (3) ◽  
pp. 320-323 ◽  
Author(s):  
Yong Ahn ◽  
Sang-Ho Lee ◽  
Woo-Min Park ◽  
Ho-Yeon Lee

✓ The purpose of this study was to determine the efficacy and feasibility of posterolateral percutaneous endoscopic lumbar foraminotomy (PELF) for foraminal or lateral exit zone stenosis of the L5—S1 level in the awake patient. Twelve consecutive patients with L5—S1 foraminal stenosis and associated leg pain underwent PELF between May 2001 and July 2002. Under fluoroscopic guidance, posterolateral endoscopic foraminal decompression was performed using a bone reamer, endoscopic forceps, and a laser. Using this new technique, the authors removed part of the hypertrophied superior facet, thickened ligamentum flavum, and protruded disc compressing the exiting (L-5) nerve root. Clinical outcome was measured using the Macnab criteria. The mean follow-up period was 12.9 months. All the patients were discharged within 24 hours. Satisfactory (excellent or good) results were demonstrated in 10 patients. There was no complication. The PELF procedure provides a simple alternative for treating lumbar foraminal or lateral exit zone stenosis in selected cases. The authors found that the posterolateral endoscopic approach to the L5—S1 foramen was usually possible and that using a bone reamer to undercut the superior facet was effective.


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