Micafungin Is Extremely Effective Against Fungal Infections Complicating Hematological Malignancies: Report of a Multicenter Study by N-FISH (Niigata Fungal Infection Study Group in Hematology).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5350-5350
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Yoshinobu Seki ◽  
Kazue Takai ◽  
Koji Nikkuni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Multicenter Study ◽  
Liver Dysfunction ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
The United States ◽  
Study Group ◽  
The Mean ◽  
Infection Study

Abstract [Background]Micafungin (MCFG) is a candin antifungal agent, and was marketed in Dec. 2002 in Japan and in Apr. 2005 in the United States. The Niigata Fungal Infection Study Group in Hematology (N-FISH) performed a multicenter prospective study to clarify the therapeutic effects of MCFG on deep fungal infections complicating hematological malignancies. [Methods]A total of 36 pts. who had been treated in centers belonging to N-FISH between Oct. 2003 and Apr. 2005 were included in this study. They consisted of 14 men and 22 women with a mean age of 53.5 years: 14 pts. with AML, 10 pts. with malignant lymphoma, 6 pts. with ALL, and 6 pts with other diseases. They had a proven fungal infection, or were suspected of having a fungal infection because of fever unresponsive to antimicrobial agents or from laboratory data. Three of them had a proven infection, and 33 were suspected of having a fungal infection. Three of these 33 pts. failed to respond to fluconazole. As a rule, MCFG was administered for more than 14 days until infectious symptoms improved or disappeared. When MCFG was judged ineffective because of the worsening of clinical symptoms despite the administration of MCFG, or when the administration of MCFG was judged difficult because of adverse effects, the drug was discontinued or replaced by other drugs. Two pts. orally received amphotericin B syrup singly. [Results]The mean dose of MCFG was 2.6 mg/kg (1.5–4.2 mg/kg), and the mean duration of administration was 15.9 days (5–85 days). Complete or partial response was achieved in 31 (86.1%) of the 36 pts., who showed improvements in infectious symptoms. In 4 pts, MCFG was discontinued because of insufficient effects. There were no breakthrough fungal infections within 7 days after the completion of MCFG therapy. Of the 36 pts., 31 (86.1%) and 24 (66.7%) survived 1 and 3 months after MCFG therapy, respectively. The cause of death was exacerbation of the primary disease, and not exacerbation or the onset of a fungal infection. Eight adverse events occurred in 7 pts.: hypoglycemia in 1, liver dysfunction in 3, eosinophilia in 1, kidney dysfunction in 2, and hypokalemia in 1. In 1 of the 3 pts. with liver dysfunction (grade 3), MCFG therapy was discontinued, with rapid improvement of the liver dysfunction. All other adverse events were mild, allowing continued MCFG therapy. [Conclusion]This multicenter study demonstrated the effectiveness and safety of MCFG therapy for deep fungal infections complicating hematological malignancies. The results suggest that MCFG should be promptly used for fever associated with a fungal infection complicating hematological malignancies.

First Line Antifungal Treatment with Caspofungin of Oncohemopatic Patients. A Single Centre Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5271-5271 ◽  
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Luigi Gugliotta
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Ct Scan ◽  
Mechanism Of Action ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Drugs ◽  
Severe Neutropenia ◽  
First Line ◽  
The Mean

Abstract Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia and among them fungal infections are the most difficult to treat and a major cause of mortality. The availability of a new class of antifungal drugs (echinocandins) could improve the chance of cure. Caspofungin (Caspo) is the first drug which is able to destroy the fungal cell wall. Since January 2004 we have treated 28 consecutive adult oncohemopatic and neutropenic pts with Caspo as first line therapy. In case of persistent fever (4 days) despite broad spectrum antibiotic therapy (association of Tazobactam/Piperacillin, Amikacin with or without Vancomycin) with negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test (this test is available at our Centre since February 2006) were performed. In the presence of any other sign or symptom we performed any other test according to the physicyan’s choice. In case of possible, probable or proven fungal infection (according to the EORTC criteria) Caspo was administered at the dosage of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. The pts were 15 males and 13 females; the mean age was 46 yrs (range 18–66 yrs). The diagnoses were: acute myeloid leukemia 13, acute lymphoblastic leukemia 5, multiple myeloma 2, lymphoma 8; the disease’s phases were: onset 9, complete remission 11, relapse 2, resistant 6. Six pts received an allogeneic and 4 an autologous BMT; the other pts received an induction or consolidation or rescue chemotherapy course. All the pts had severe neutropenia and the fungal infections were proven in 3 cases (2 aspergillus spp and 1 aspergillus fumigatus), probable in 3 cases and possible in 22 cases. The first site of infection was the lung in 27 pts and paranasal sinuses in 1 patient. CT scan was positive (halo sign, air-crescent sign or cavitation) in all the pts with a lung localization. The mean time of treatment was 18 days (range 6–21 days). The treatment was not discontinued for anyone because of adverse events and no modifications of the dosage were necessary. All the pts submitted to an allogeneic BMT received concomitant therapy with Cyclosporine A and we had not to change the dosage and we did not found any renal or liver alterations. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion as premedication. No breakthrough fungal infections were found. The infection was cured in 24/28 pts; 4 pts died for fungal infection progression (3 with a progression to the brain and in 1 case the infection remained in the lungs). For all the cured pts there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial fact for the resolution of the infection. Among the 24 cured patients 8 died later: 5 for hematologic disease and 3 for sepsis during malignant disease recurrence. In 2 cases there was the recurrence of the fungal infection despite the secondary prophylaxis with Caspo. In conclusion we can say we have a new treatment option for fungal infections in neutropenic pts with a new mechanism of action; this option seems safe, it does not preclude any other treatment (such as Cyclosporine), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost is lower than other antifungal treatments.

Antifungal Treatment with Caspofungin: A Single Centre Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5386-5386
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Luigi Gugliotta
Keyword(s):  
Adverse Events ◽  
Antibiotic Therapy ◽  
Fungal Infection ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
The Other ◽  
Broad Spectrum Antibiotic ◽  
Persistent Fever ◽  
Neutropenic Patients ◽  
The Mean

Abstract Infections are the main complication for patients with hematologic diseases and severe neutropenia and among them fungal infections are the most diffucult to treat and a major cause of mortality for these patients. Now we have a new antifungal class, Echinocandins which work with a new and different mechanism of action regarding azoles and amphotericin B, so we wanted to verify the tolerability and efficacy of Caspofungin (Caspo). From January 2004 until now we have treated 15 consecutive oncohemopatic and neutropenic patients admitted at our Institution. The schedule of treatment was: in case of persistent fever (at least 4 days) during broad spectrum antibiotic therapy a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum and blood cultures were performed. In case of positivity of one or more of these findings suggesting for invasive fungal disease, Caspofungin was administered at the dosage of 70 mg i.v. on the first day and 50 mg i.v. from the second day; the infusion time was 1 hour. The patients were 10 males and 5 females, the mean age was 46 yrs (range 19–60 yrs). The diagnoses were: acute myeloid leukemia 8, acute lymphoblastic leukemia 3, lymphoma 4; the disease’s phases were: onset 3, first remission 3, remission>I 2, partial remission 5, relapse 1, resistant 1. Two patients received an allogeneic BMT, 1 an autologous BMT, the other patients an induction or consolidation or rescue chemotherapy course. In four cases Caspo was administered as secondary prophylaxis of a previous invasive fungal infection while for the other patients Caspo was administered for persistent fever and at least one lesion of the lungs or other organs with no evidence of bacterial or viral infection. The mean time of treatment was 18 days (range 6–21 days); the treatment was not discontinued for anyone of them because of adverse events; the dosage of Caspo was not changed for anyone. For the 2 allogeneic BMT Cyclosporine A administration was not changed and we did not found any renal or liver alterations. All the patients received a concomitant broad spectrum antibiotic therapy (association of Tazobactam/Piperacilline, Amikacine and Vancomycin) and for none of them we registered any liver or renal disfunction. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion. We did not seen breakthrough fungal infections. In 2 patients a proven fungal infection (Aspergillus fumigatus and Aspergillus spp) was demonstrated so the other cases remained probable or possible infections. No progression of the infection was seen. All the infections, except one, resolved; one patient died after 6 days of antifungal treatment for leukemia progression. Five patients died: 4 for leukemia and 1 for bacterial infection (Pseudomonas aeruginosa) after the fungal infection. In conclusion now we have a new treatment option for fungal infections in neutropenic patients and this option is safe, it does not preclude any other treatment (such as CsA), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost of the drug is lower than other antifungal treatments. According to these preliminary data we have decided to continue this experience to verify them in a larger cohort of patients.

Fluconazole Treatment of Neonates and Infants with Severe Fungal Infections

1997 ◽  
Vol 25 (4) ◽  
pp. 214-218 ◽  
Author(s):  
AN Gürpinar ◽  
E Balkan ◽  
N Kiliç ◽  
İ Kiriştioǧlu ◽  
İ Avşar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Clinical Response ◽  
Fungal Infections ◽  
Efficacy And Safety ◽  
Duration Of Therapy ◽  
Day Range ◽  
The Mean ◽  
Neonates And Infants

A total of 24 neonates and infants, aged from 2 days to 10 months, received treatment with intravenous fluconazole for microbiologically documented or presumed fungal infection. The mean fluconazole dosage was 6 mg/kg/day (range 2 –16 mg/kg/day) and the mean duration of therapy was 25 days (range 5–72 days). Efficacy was evaluated in neonates with proven fungal infections, as documented by the presence of pathogen at baseline. A positive clinical response was achieved in 23 of the 24 clinically evaluable patients (96%); eradication of the fungal organism was also achieved in 23 of the 24 evaluable patients (96%). Adverse events occurred in two patients (8%) but therapy was not discontinued in either patient. The present results confirm the efficacy and safety of fluconazole in the treatment of neonates and infants with severe fungal infections.

First Line Treatment of Probable and Proven Invasive Aspergillosis with Caspofungin in Oncohemopatic Patients. A Single Centre Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4836-4836
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Barbara Gamberi ◽  
Annalisa Imovilli ◽  
Cristiano Carbonelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Cyclosporin A ◽  
Ct Scan ◽  
Fungal Infections ◽  
Severe Neutropenia ◽  
Cell Transplant ◽  
First Line ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia. In particular fungal infections are the most difficult to treat and represent a major cause of mortality. Caspofungin (Caspo) is the first drug which is able to inhibit the growth of the fungal cell wall. Since January 2004 we have treated 64 consecutive adult neutropenic pts with Caspo as first line therapy. In the setting of persistent fever (3 days) despite broad spectrum antibiotic therapy and negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test were performed. In the setting of probable or proven fungal infection (according to the revised EORTC criteria and Cornely CID 2007) Caspo was administered at the dose of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. They were 35 males and 29 females; the mean age was 56 yrs (range 19–77 yrs). The diagnoses were: acute leukemia 46 (72%), myeloma 2 (3%), lymphoma 14 (22%) and chronic leukemia 2 (3%); the disease’s phases were: new onset 26 (41%), remission 16 (24%), relapse 22 (35%). Thirteen pts received an allogeneic and 5 an autologous hematopoietic stem cell transplant; the other pts received an induction or consolidation or rescue chemotherapy course. Fungal infections were proven in 13 cases (20% including 11 aspergillus spp, 1 aspergillus fumigatus, 1 G. capitatum) and probable in 51 cases (80%). The first site of infection was the lung in 63 pts (98%) and paranasal sinuses in 1 patient (2%). CT scan was positive (halo sign or air-crescent sign) in all the pts with a lung localization, while the chest X-ray was positive in 40% of them. BAL was performed in 31 pts. The mean time of treatment was 18 days (range 13–25 days). Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion of Caspo were seen, and it was not necessary to administer any drug before the infusion as premedication. The global (partial and complete) response was 55/64 (86%); 9 pts died for fungal infection. The efficacy responses were generally similar for probable and proven infections. No breakthrough fungal infections were found. All surviving patients, upon discharge from the hospital, received oral treatment with Voriconazole or Posaconazole. For all the cured pts, there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial factor for the resolution of the infection. Among the 55 responsive patients, 25 (45%) died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 cases there was the recurrence of the fungal infection. In conclusion the resolution rate of the infections is very high (86%); Caspo seems safe, it does not preclude any other treatment (such as Cyclosporin A), it is well tolerated and the cost is lower than other antifungal treatments.

Palifermin in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation (HSCT): The Italian Early Access Program (EAP).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5236-5236
Author(s):  
Laura M. Cavagna ◽  
Gaetano Bonifacio ◽  
Emanuele Angelucci ◽  
Alessandro Fanni ◽  
Giuseppe Milone ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Adverse Events ◽  
Interim Analysis ◽  
Hematological Malignancies ◽  
Hematologic Malignancies ◽  
World Health ◽  
High Dose ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Oral mucositis (OM) is an acute, severe and often dose-limiting toxicity in patients undergoing HSCT. OM significantly affects functional status and patients’ quality of life; however no effective therapy was available for this condition. Palifermin (Kepivance®) is a human keratinocyte growth factor (KGF) produced by recombinant DNA technology. KGF binds to its receptor on epithelial cells, stimulating their proliferation, differentiation, and migration. Palifermin has been shown to decrease the incidence and duration of severe OM in patients with hematologic malignancies receiving myelotoxic therapy and HSCT. In Italy, compassionate use protocols are considered EAP and are regulated by a decree issued by the Ministry of Health (MoH) on May 8th 2003. The objective of the Decree is to ensure that patients have access to experimental therapies outside clinical trials, when no valid therapeutic alternative exists. Approval is granted in case of serious or rare diseases or life-threatening conditions. After Ethical Committee (EC) approval and notification to MoH, the drug can be supplied in response to an unsolicited request from a physician. The drug is then administered under the physician’s direct responsibility. During EAP, the Decree allows collection of the patient’s data similar to an observational trial. From July 2005 through July 2006 a total of 26 centers have requested the drug and obtained approval from local EC. Each center collected the following data on a case report form: vital signs, disease status and treatment, palifermin administration, mucositis, analgesic use, parenteral supplementation, common laboratory tests and duration of hospitalization. A total of 175 adults patients with hematological malignancies treated with autologous SCT participated in the EAP. In an interim analysis, data from 41 patients (24 men; 17 women; median age 52.44) were analyzed. The most common diagnoses were multiple myeloma (MM) (n=16) and non-Hodgkin lymphoma (NHL) (n=15). Conditioning therapy and supportive care were administered according to standard institutional practice (high-dose melphalan for MM and the BEAM regimen for NHL). Palifermin 60 mcg/kg/day was given intravenously on 3 consecutive days before the conditioning regimen and on 3 days starting on the day of stem cell infusion. OM was evaluated daily for 28 days after transplantation or until severe OM resolution using the five-grade World Health Organization (WHO) oral-toxicity scale. Safety was assessed on the basis of the incidence of adverse events. The incidence of severe OM (Grade 3–4) was 17% and the mean duration was 2.2 ± 3.5 days (CI, 1.1–3.3) in patients with OM Grade 0–4 while in patients with OM G3-4 the mean duration was 6.9 ± 2.5 (CI, 4.5–9.2). Adverse events (mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration) were mild to moderate in severity and were transient. The frequency of adverse events was consistent with those observed in clinical trials. In conclusion, the Italian EAP experience with palifermin suggested that results were consistent with those of pivotal studies in patients with hematologic malignancies undergoing HSCT. From the results of the interim analysis of the Italian EAP, the use of palifermin in this setting appears to be feasible and was widely accepted by participating physicians and patients.

Clinical Safety of Long-Term Intravenous Itraconazole for the Treatment of Invasive Fungal Infection In Severely Ill Patients with Hematological Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4943-4943
Author(s):  
Yaping Xie ◽  
Shenxian Qian ◽  
Daquan Gao ◽  
Xilian Huang ◽  
Pengfei Shi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Hematological Malignancies ◽  
Liver Enzymes ◽  
Conflicts Of Interest ◽  
Oral Formulation ◽  
Clinical Safety ◽  
Severe Adverse Events

Abstract Abstract 4943 The clinical safety of intravenous itraconazole use exceeding 14 days is unknown. However, many cases need further treatment, but the absorption of itraconazole oral in severely ill patients is variable and unpredictable. Gastric acidity and food influence the absorption of oral formulation. The intravenous formulation, on the other hand, achieves adequate blood levels more rapidly and its bioavailability is predictable and invariable compared to the oral formulation. We performed this study to investigate the clinical safety of long-term intravenous itraconazole for the treatment of invasive fungal infection (IFI) in severely ill patients with hematological malignancies. 20 patients (median age, 70 years; range, 38–82 years) with hematological malignancies who had met the IFI inclusion criteria were enrolled. All the infection sites were the lung. These patients were given intravenous itraconazole for 14 days. There were significant effective but the lesions were not fully absorbed and no severe adverse events were found. So the long-term intravenous itraconazole therapy was enabled. Clinical efficacy and adverse events were recorded. Itraconazole 200 mg via intravenous infusion (administered over 1 hour) twice a day for 4 doses followed by 200 mg once a day until the lesions was fully absorbed. The treatment median time was 27(18-58) days. During this period, closely monitor changes in vital signs, chest CT, liver enzymes, renal function, electrocardiogram and electrolytes were assessed. We found that the patients achieved composite endpoints including survival, defervescence and undetectable lesions, except one patient died of primary disease - acute myeloid leukemia. Treatment-related adverse events were found in 7 patients (35%) during the study and none of them were severe adverse events. Such as hypokalemia (10.0%), gastrointestinal disorders (10.0%), elevation of liver enzymes (10.0%) and pleural effusion (5.0%). All the adverse events occurred during the first two weeks of the treatment and no significant exacerbation in the following days. In conclusion, long-term intravenous itraconazole therapy was effective for IFI and the drug-related adverse events have been shown to be generally predictable and manageable. Disclosures: No relevant conflicts of interest to declare.

Invasive fungal infections are associated with severe depletion of circulating RANTES

2005 ◽  
Vol 54 (11) ◽  
pp. 1017-1022 ◽  
Author(s):  
Michael Ellis ◽  
Basel al-Ramadi ◽  
Ulla Hedström ◽  
Hussain Alizadeh ◽  
Victor Shammas ◽  
...  
Keyword(s):  
T Cell ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Host Response ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Time Of Death ◽  
Haematological Malignancies ◽  
Platelet Counts ◽  
The Mean

Serum RANTES (regulated on activation, normal T-cell expressed and secreted) concentrations were measured in 14 patients who had haematological malignancies and developed invasive fungal infections (three of them definite, eight probable and three possible). RANTES levels fell substantially from pre-chemotherapy values at the start of and throughout the fungal infection, and recovered in patients who survived the fungal infection. However, in patients who died from the invasive fungal infection, RANTES levels did not recover. For survivors the mean ± sd levels for RANTES were 7656 ± 877 pg ml−1 on the day prior to chemotherapy, 3723 ± 2443 pg ml−1 on the first day of fungal infection diagnosis (significantly different from baseline; P = 0.001) and 9078 ± 2256 pg ml−1 at recovery from the fungal infection (significantly different from lowest value; P < 0.0001). Platelet counts were closely correlated with the RANTES levels (r = 0.63, P < 0.001). The RANTES concentrations for the three patients who died were similar to those who survived at all equivalent timepoints, but were significantly lower at the time of death (792 ± 877) compared to the values at recovery for survivors (P = 0.005). The finding that patients who died from an invasive fungal infection had very low platelet counts and RANTES concentrations suggests that these could play a role in host response to such infections.

scholarly journals Efficacy and adverse events related to the initial dose of methimazole in children and adolescents with Graves’ disease

2021 ◽  
Vol 26 (3) ◽  
pp. 199-204
Author(s):  
Hyun Gyung Lee ◽  
Eun Mi Yang ◽  
Chan Jong Kim
Keyword(s):  
Adverse Events ◽  
Children And Adolescents ◽  
Liver Dysfunction ◽  
Initial Dose ◽  
Graves Disease ◽  
Group A ◽  
The Mean ◽  
Group B ◽  
The Relationship ◽  
Mean Time

Purpose: The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment.Methods: We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: <0.4 mg/kg/day (group A; n=32); 0.4–0.7 mg/kg/day (group B; n=39); and >0.7 mg/kg/day (group C; n=28).Results: The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively).Conclusion: The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.

Sign in / Sign up

Export Citation Format

Share Document