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1.
Viruses ; 16(2)2024 01 25.
Article in English | MEDLINE | ID: mdl-38399957

ABSTRACT

In 2019-2020, dengue virus (DENV) type 4 emerged to cause the largest DENV outbreak in Paraguay's history. This study sought to characterize dengue relative to other acute illness cases and use phylogenetic analysis to understand the outbreak's origin. Individuals with an acute illness (≤7 days) were enrolled and tested for DENV nonstructural protein 1 (NS1) and viral RNA by real-time RT-PCR. Near-complete genome sequences were obtained from 62 DENV-4 positive samples. From January 2019 to March 2020, 799 participants were enrolled: 253 dengue (14 severe dengue, 5.5%) and 546 other acute illness cases. DENV-4 was detected in 238 dengue cases (94.1%). NS1 detection by rapid test was 52.5% sensitive (53/101) and 96.5% specific (387/401) for dengue compared to rRT-PCR. DENV-4 sequences were grouped into two clades within genotype II. No clustering was observed based on dengue severity, location, or date. Sequences obtained here were most closely related to 2018 DENV-4 sequences from Paraguay, followed by a 2013 sequence from southern Brazil. DENV-4 can result in large outbreaks, including severe cases, and is poorly detected with available rapid diagnostics. Outbreak strains seem to have been circulating in Paraguay and Brazil prior to 2018, highlighting the importance of sustained DENV genomic surveillance.


Subject(s)
Dengue Virus , Dengue , Humans , Dengue Virus/genetics , Dengue/diagnosis , Dengue/epidemiology , Paraguay/epidemiology , Phylogeny , Acute Disease , Genotype , Disease Outbreaks
2.
Pediatr Blood Cancer ; 70(8): e30395, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37178438

ABSTRACT

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.


Subject(s)
Antiemetics , Antineoplastic Agents , Neoplasms , Adult , Child , Humans , Antiemetics/adverse effects , Antineoplastic Agents/adverse effects , Nausea/chemically induced , Nausea/drug therapy , Nausea/prevention & control , Neoplasms/complications , Neoplasms/drug therapy , Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/prevention & control
3.
PLoS Negl Trop Dis ; 17(2): e0010750, 2023 02.
Article in English | MEDLINE | ID: mdl-36848385

ABSTRACT

BACKGROUND: Dengue is the most common vector-borne viral disease worldwide. Most cases are mild, but some evolve into severe dengue (SD), with high lethality. Therefore, it is important to identify biomarkers of severe disease to improve outcomes and judiciously utilize resources. METHODS/PRINCIPAL FINDINGS: One hundred forty-five confirmed dengue cases (median age, 42; range <1-91 years), enrolled from February 2018 to March 2020, were selected from an ongoing study of suspected arboviral infections in metropolitan Asunción, Paraguay. Cases included dengue virus types 1, 2, and 4, and severity was categorized according to the 2009 World Health Organization guidelines. Testing for anti-dengue virus IgM and IgG and serum biomarkers (lipopolysaccharide binding protein and chymase) was performed on acute-phase sera in plate-based ELISAs; in addition, a multiplex ELISA platform was used to measure anti-dengue virus and anti-Zika virus IgM and IgG. Complete blood counts and chemistries were performed at the discretion of the care team. Age, gender, and pre-existing comorbidities were associated with SD vs. dengue with/without warning signs in logistic regression with odds ratios (ORs) of 1.07 (per year; 95% confidence interval, 1.03, 1.11), 0.20 (female; 0.05,0.77), and 2.09 (presence; 1.26, 3.48) respectively. In binary logistic regression, for every unit increase in anti-DENV IgG in the multiplex platform, odds of SD increased by 2.54 (1.19-5.42). Platelet count, lymphocyte percent, and elevated chymase were associated with SD in a combined logistic regression model with ORs of 0.99 (1,000/µL; 0.98,0.999), 0.92 (%; 0.86,0.98), and 1.17 (mg/mL; 1.03,1.33) respectively. CONCLUSIONS: Multiple, readily available factors were associated with SD in this population. These findings will aid in the early detection of potentially severe dengue cases and inform the development of new prognostics for use in acute-phase and serial samples from dengue cases.


Subject(s)
Flavivirus , Severe Dengue , Adult , Female , Humans , Antibodies, Viral , Biomarkers , Chymases , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Immunoglobulin M , Severe Dengue/diagnosis , Male
4.
Pediatr Blood Cancer ; 69(12): e30001, 2022 12.
Article in English | MEDLINE | ID: mdl-36221901

ABSTRACT

This clinical practice guideline provides recommendations for preventing acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. The recommendations are based on two systematic reviews of randomized controlled trials evaluating interventions to prevent (1) acute phase CINV and (2) delayed phase CINV. Recommendations for acute phase and delayed phase CINV prophylaxis are made for patients receiving chemotherapy of varying emetogenicity, as well as for patients not able to receive dexamethasone or a neurokinin-1 receptor antagonist. Evidence gaps, including antiemetic safety and optimal dosing, were identified.


Subject(s)
Antiemetics , Antineoplastic Agents , Neoplasms , Child , Humans , Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Nausea/chemically induced , Nausea/drug therapy , Nausea/prevention & control , Neoplasms/drug therapy , Vomiting/chemically induced , Vomiting/prevention & control , Vomiting/drug therapy , Randomized Controlled Trials as Topic , Systematic Reviews as Topic
5.
Support Care Cancer ; 30(11): 8855-8869, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35953731

ABSTRACT

PURPOSE: To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients. METHODS: We conducted a systematic review of randomized trials evaluating interventions to prevent acute CINV. Outcomes assessed were complete chemotherapy-induced vomiting (CIV) control, complete chemotherapy-induced nausea (CIN) control, complete CINV control, and discontinuation of antiemetics due to adverse effects. RESULTS: The search identified 65,172 citations; 744 were evaluated at full-text, and 295 (25 pediatric) met eligibility criteria. In patients receiving highly emetogenic chemotherapy (HEC), complete CIV (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.05-1.44) and CIN (RR 1.34, 95% CI 1.10-1.62) control improved when olanzapine was added. The addition of a neurokinin-1 receptor antagonist (NK1RA) to a corticosteroid plus a serotonin-3 receptor antagonist (5HT3RA) also improved complete CIV (RR 1.11, 95% CI 1.08-1.14) and CIN (RR 1.05, 95% CI 1.01-1.08) control. Compared to granisetron/ondansetron, palonosetron provided improved complete CIV control when the 5HT3RA was given alone or when combined with dexamethasone. In patients receiving moderately emetogenic chemotherapy (MEC), dexamethasone plus a 5HT3RA improved complete CIV control compared to a 5HT3RA alone (RR 1.29, 95% CI 1.21-1.39). Only a single meta-analysis evaluating the safety outcome was possible. CONCLUSIONS: For patients receiving HEC, various antiemetic regimens improved CIV and CIN control. For patients receiving MEC, administration of a 5HT3RA plus dexamethasone improved CIV control. Analysis of antiemetic safety was constrained by lack of data.


Subject(s)
Antiemetics , Antineoplastic Agents , Neoplasms , Adult , Humans , Child , Antiemetics/therapeutic use , Neoplasms/drug therapy , Nausea/chemically induced , Nausea/prevention & control , Nausea/drug therapy , Vomiting/chemically induced , Vomiting/prevention & control , Vomiting/drug therapy , Dexamethasone/therapeutic use , Antineoplastic Agents/adverse effects
6.
Eur J Cancer ; 154: 92-101, 2021 09.
Article in English | MEDLINE | ID: mdl-34252760

ABSTRACT

PURPOSE: To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients. METHODS: We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis. RESULTS: We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31-0.76; palifermin RR 0.81 and 95% CI 0.69-0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27-0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects. CONCLUSIONS: Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620-750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/therapy , Practice Guidelines as Topic , Stomatitis/prevention & control , Adult , Child , Cryotherapy , Humans , Low-Level Light Therapy , Oropharynx , Radiotherapy/adverse effects , Stomatitis/etiology
7.
Pediatr Blood Cancer ; 68(5): e28947, 2021 05.
Article in English | MEDLINE | ID: mdl-33686754

ABSTRACT

This 2021 clinical practice guideline update provides recommendations for preventing anticipatory chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. Recommendations are based on systematic reviews that identified (1) if a history of acute or delayed CINV is a risk factor for anticipatory CINV, and (2) interventions for anticipatory CINV prevention and treatment. A strong recommendation to optimize acute and delayed CINV control in order to prevent anticipatory CINV is made. Conditional recommendations are made for hypnosis, systematic desensitization, relaxation techniques, and lorazepam for the secondary prevention of anticipatory CINV. No recommendation for the treatment of anticipatory CINV can be made.


Subject(s)
Antineoplastic Agents/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Nausea/prevention & control , Neoplasms/drug therapy , Vomiting, Anticipatory/prevention & control , Child , Child, Preschool , Female , Humans , Infant , Male , Nausea/chemically induced , Vomiting, Anticipatory/psychology
8.
BMJ Evid Based Med ; 26(6): 320-326, 2021 12.
Article in English | MEDLINE | ID: mdl-32868288

ABSTRACT

Our purpose was to compare conventional meta-analysis and network meta-analysis to evaluate the efficacy of different prophylactic systemic antibiotic classes in patients undergoing chemotherapy or haematopoietic stem cell transplant (HSCT). We included randomised trials if patients had cancer or were HSCT recipients and the intervention was systemic antibacterial prophylaxis. Three types of control groups were used: (1) placebo, no antibiotic and non-absorbable antibiotic separately; (2) placebo and no antibiotic combined; and (3) all three combined. These gave different network geometries. Strategies synthesised were fluoroquinolone, trimethoprim-sulfamethoxazole, cephalosporin and parenteral glycopeptide versus control groups. In total 113 trials met the eligibility criteria. Where treatment effects could be estimated with both conventional and network meta-analysis, values were generally similar. However, where events were sparse, network meta-analysis could be more precise. For example, trimethoprim-sulfamethoxazole versus placebo for infection-related mortality showed a relative risk ratio (RR) of 0.55, 95% CI (0.21 to 1.44) with conventional, and RR 0.43, 95% credible region (0.20 to 0.82) with network meta-analysis. Cephalosporin versus fluoroquinolone was comparable only indirectly using the network approach and yielded RR 0.59, 95% credible region (0.28 to 1.20) to reduce bacteraemia. Incoherence (difference between direct and indirect estimates raising concerns about network meta-analysis validity) was observed with network geometry where control groups were separated, but not where control groups were combined. In this situation, conventional and network meta-analysis yielded similar results in general. Network meta-analysis results could be more precise when events were rare. Some analysis could only be performed with the network approach. These results identify scenarios in which network meta-analysis may be advantageous.


Subject(s)
Hematopoietic Stem Cell Transplantation , Neoplasms , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Humans , Neoplasms/complications , Neoplasms/therapy , Network Meta-Analysis
9.
Pediatr Blood Cancer ; 67(12): e28716, 2020 12.
Article in English | MEDLINE | ID: mdl-32970373

ABSTRACT

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy-induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose-finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT3 antagonist and five in conjunction with a 5HT3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta-analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research.


Subject(s)
Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Dexamethasone/therapeutic use , Neoplasms/drug therapy , Vomiting/prevention & control , Child , Dose-Response Relationship, Drug , Humans , Neoplasms/pathology , Vomiting/chemically induced , Vomiting/pathology
10.
Psychosomatics ; 61(2): 145-153, 2020.
Article in English | MEDLINE | ID: mdl-31864662

ABSTRACT

BACKGROUND: Psychiatric disorders are common in cancer patients and impact outcomes. Impact on cancer care cost needs study to develop business case for psychosocial interventions. OBJECTIVE: To evaluate the impact of preexisting psychiatric comorbidities on total cost of care during 6 months after cancer diagnosis. METHODS: This retrospective cohort study examined patients diagnosed with cancer between January 1, 2009, and December 31, 2014, at one National Cancer Institute-designated cancer center. Patients who received all cancer treatment at the study site (6598 of 11,035 patients) were included. Patients were divided into 2 groups, with or without psychiatric comorbidity, based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Total costs of care during the first 6 months of treatment were based on standardized costs adjusted to 2014 dollars, determined by assigning Medicare reimbursement rates to professional billed services and applying appropriate cost-to-charge ratios. Quantile regression models with covariate adjustments were developed to assess the effect of psychiatric comorbidity across the distribution of costs. RESULTS: Six hundred ninety-eight (10.6%) of 6598 eligible patients had at least one psychiatric comorbidity. These patients had more nonpsychiatric Elixhauser comorbidities (mean 4 vs. 3). Unadjusted total cancer care costs were higher for patients with psychiatric comorbidity (mean [standard deviation]: $51,798 [$74,549] vs. $32,186 [$45,240]; median [quartiles]: $23,871 [$10,705-$57,338] vs. $19,073 [$8120-$38,230]). Quantile regression models demonstrated that psychiatric comorbidity had significant incremental effects at higher levels of cost: 75th percentile $8629 (95% confidence interval: $3617-13,642) and 90th percentile $42,586 (95% confidence interval: $25,843-59,330). CONCLUSIONS: Psychiatric comorbidities are associated with increased total cancer costs, especially in patients with very high cancer care costs, representing an opportunity to develop mitigation strategies.


Subject(s)
Health Care Costs/statistics & numerical data , Mental Disorders/economics , Neoplasms/economics , Psychosocial Intervention/economics , Cancer Care Facilities/economics , Cohort Studies , Comorbidity , Humans , Mental Disorders/complications , Mental Disorders/therapy , Neoplasms/complications , Neoplasms/therapy , Retrospective Studies
11.
Lancet Child Adolesc Health ; 4(2): 141-150, 2020 02.
Article in English | MEDLINE | ID: mdl-31866182

ABSTRACT

Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.


Subject(s)
Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Hearing Loss/chemically induced , Neoplasms/drug therapy , Thiosulfates/therapeutic use , Adolescent , Antineoplastic Agents/therapeutic use , Child , Cisplatin/therapeutic use , Female , Hearing Loss/drug therapy , Humans , Male , Neoplasms/pathology , Ototoxicity , Prognosis , Randomized Controlled Trials as Topic , Survival Rate
12.
Clin Infect Dis ; 71(1): 226-236, 2020 06 24.
Article in English | MEDLINE | ID: mdl-31676904

ABSTRACT

BACKGROUND: Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT. METHODS: An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. RESULTS: The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. CONCLUSIONS: We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.


Subject(s)
Bacteremia , Hematopoietic Stem Cell Transplantation , Neoplasms , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Bacteremia/drug therapy , Bacteremia/prevention & control , Child , Humans , Levofloxacin , Neoplasms/drug therapy , Neoplasms/therapy
13.
Cancer Med ; 8(10): 4536-4546, 2019 08.
Article in English | MEDLINE | ID: mdl-31274245

ABSTRACT

PURPOSE: To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT). METHODS: We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia. RESULTS: Of 20 984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified. CONCLUSIONS: Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required.


Subject(s)
Antibiotic Prophylaxis/methods , Antineoplastic Agents/adverse effects , Bacteremia/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/therapy , Adult , Anti-Bacterial Agents/therapeutic use , Bacteremia/prevention & control , Child , Humans , Randomized Controlled Trials as Topic , Treatment Outcome
14.
Lancet Child Adolesc Health ; 3(8): 578-584, 2019 08.
Article in English | MEDLINE | ID: mdl-31160205

ABSTRACT

The identification of preventive interventions that are safe and effective for cisplatin-induced ototoxicity is important, especially in children because hearing loss can impair speech-language acquisition development. Previous randomised trials assessed systemic drugs such as amifostine, sodium diethyldithiocarbamate or disulfiram, and sodium thiosulfate. Amifostine, sodium diethyldithiocarbamate, and disulfiram did not show hearing preservation. Paediatric trials assessing sodium thiosulfate showed efficacy in terms of hearing protection. The SIOPEL 6 trial consisted solely of patients with localised hepatoblastoma and no effects on survival were shown. In the ACCL0431 trial, which included heterogeneous patients, a post-hoc analysis showed significantly worse overall survival among patients who had disseminated disease receiving sodium thiosulfate than among controls, but not among those with localised disease. Intratympanically administered drugs have mainly been assessed in adults and include N-acetylcysteine and dexamethasone. Inconsistent effects of these drugs were identified but these studies were limited by design, small sample size, and statistical approach. Future studies of systemic drugs will need to consider the measurement of disease outcomes through study design and sample size, and ototoxicity endpoints should be harmonised to enhance comparability between trials.


Subject(s)
Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Neoplasms/drug therapy , Ototoxicity/etiology , Ototoxicity/prevention & control , Acetylcysteine/therapeutic use , Adolescent , Amifostine/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Chelating Agents/therapeutic use , Child , Cytoprotection , Dexamethasone/therapeutic use , Disulfiram/therapeutic use , Ditiocarb/therapeutic use , Humans , Thiosulfates/therapeutic use
15.
Pediatr Blood Cancer ; 66(5): e27646, 2019 05.
Article in English | MEDLINE | ID: mdl-30729654

ABSTRACT

This clinical practice guideline (CPG) provides clinicians with recommendations regarding chemotherapy emetogenicity classification in pediatric oncology patients. This information is critically important for the appropriate selection of antiemetic prophylaxis. Recommendations are based on a systematic review limited to pediatric patients and a framework for classification when antiemetic prophylaxis is provided. Findings of 87 publications informed the emetogenicity classification of 49 single-agent and 13 combination-agent regimens. Information required for the classification of many chemotherapies commonly administered to pediatric patients is lacking. In the absence of pediatric data, consultation of methodologically sound CPGs aimed at adult oncology patients may be appropriate.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/classification , Nausea/chemically induced , Neoplasms/drug therapy , Practice Guidelines as Topic/standards , Vomiting/chemically induced , Child , Clinical Trials as Topic , Humans , Prognosis
16.
Pediatr Blood Cancer ; 66(1): e27471, 2019 01.
Article in English | MEDLINE | ID: mdl-30259647

ABSTRACT

Providing evidence-based supportive care for children with cancer has the potential to optimize treatment outcomes and improve quality of life. The Children's Oncology Group (COG) Supportive Care Guidelines Subcommittee conducted a systematic review to identify current supportive care clinical practice guidelines (CPGs) relevant to childhood cancer or pediatric hematopoietic stem cell transplant. Only 22 papers met the 2011 Institute of Medicine criteria to be considered a CPG. The results highlight the paucity of CPGs available to pediatric oncology healthcare professionals and the pressing need to create CPGs using current methodological standards.


Subject(s)
Neoplasms/therapy , Palliative Care/standards , Practice Guidelines as Topic/standards , Practice Patterns, Physicians'/standards , Child , Health Services Needs and Demand , Humans
17.
J Clin Oncol ; 36(31): 3162-3171, 2018 Nov 01.
Article in English | MEDLINE | ID: mdl-30216124

ABSTRACT

PURPOSE: The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. METHODS: An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. RESULTS: The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. CONCLUSION: We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.

18.
Lancet Child Adolesc Health ; 2(5): 371-378, 2018 05.
Article in English | MEDLINE | ID: mdl-30169270

ABSTRACT

Fatigue is a prevalent and distressing symptom in children and adolescents with cancer and in those who have undergone haemopoietic stem-cell transplantation. A multidisciplinary and multinational group of experts in paediatric oncology and fatigue, together with patient advocates, developed a clinical practice guideline for management of fatigue on the basis of systematic reviews that included six paediatric and 456 adult randomised studies. We used the Grading of Recommendations Assessment, Development and Evaluation approach to generate recommendations, and made strong recommendations, supported by evidence of moderate quality, for use of physical activity, relaxation, and mindfulness to reduce fatigue. When these approaches are unsuccessful or not feasible, cognitive or cognitive behavioural therapies may be offered (weak recommendation supported by evidence of moderate quality). Maturity and cognitive ability of individual patients will affect the feasibility of interventions. Systemic pharmacological approaches should not be routinely used to manage fatigue in children. Apart from identification of optimal approaches to implement recommended interventions in clinical practice, future research should also address knowledge gaps, including establishment of minimum age thresholds for interventions and inclusion of paediatric patients in randomised trials of fatigue management.


Subject(s)
Fatigue/therapy , Adolescent , Child , Fatigue/etiology , Hematopoietic Stem Cell Transplantation , Humans , Neoplasms/complications , Neoplasms/surgery , Practice Guidelines as Topic
19.
Crit Rev Oncol Hematol ; 122: 52-59, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29458789

ABSTRACT

PURPOSE: Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. METHODS: We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. RESULTS: There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. CONCLUSIONS: Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority.


Subject(s)
Exercise Therapy/methods , Exercise/physiology , Fatigue/therapy , Hematopoietic Stem Cell Transplantation/methods , Neoplasms/therapy , Fatigue/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Neoplasms/physiopathology , Quality of Life , Randomized Controlled Trials as Topic
20.
Crit Rev Oncol Hematol ; 120: 210-216, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29198334

ABSTRACT

PURPOSE: To determine whether non-physical activity mind and body practices reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients compared to control interventions. METHODS: We included randomized trials which compared non-physical activity mind and body practices compared with control interventions for the management of fatigue in cancer and HSCT patients. RESULTS: Among 55 trials (4975 patients), interventions were acupuncture or acupressure (n=12), mindfulness (n=11), relaxation techniques (n=10), massage (n=6), energy therapy (n=5), energizing yogic breathing (n=3) and others (n=8). When combined, all interventions significantly reduced fatigue severity compared to all controls (standardized mean difference -0.51, 95% confidence interval -0.73 to -0.29). More specifically, mindfulness and relaxation significantly reduced fatigue severity. CONCLUSIONS: Mindfulness and relaxation were effective at reducing fatigue severity in patients with cancer and HSCT recipients. Future studies should evaluate how to translate these findings into clinical practice across different patient groups.


Subject(s)
Fatigue/therapy , Hematopoietic Stem Cell Transplantation/methods , Mind-Body Therapies/methods , Neoplasms/therapy , Acupuncture Therapy , Fatigue/etiology , Fatigue/psychology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/psychology , Humans , Massage , Mindfulness , Neoplasms/psychology , Randomized Controlled Trials as Topic , Relaxation Therapy , Yoga
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