To test the effects of 12 weeks of honey consumption on the development of febrile neutropenia (FN) among children with acute lymphoblastic leukemia (ALL)

Patients were randomized to the order in which they received the honey or control interventions. Subjects took 2 ml (2.5 g) honey/kg body weight twice weekly for 12 weeks. In the control condition, no honey was ingested. Patients were directly observed taking the honey in the outpatient clinic to ensure compliance with the regimen. Raw and unprocessed honey was used. All patients were on standardized antibiotic prophylaxis. Patient with diabetes mellitus were excluded from the study. Blood counts were done on a weekly basis, and data analysis was done at baseline, 12 weeks, and 24 weeks. Patient who developed FN were hospitalized and treated with empiric antibiotics.

• N = 40   
• MEAN AGE = 5.4 years
• AGE RANGE = 2.5–10 years
• MALES: 50%, FEMALES: 50%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had ALL and were receiving maintenance therapy.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Egypt

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

• Randomized, crossover, open-label

• Absolute neutrophil count (ANC)
• Complete blood counts

During the control period, the hemoglobin, ANC, and platelet counts decreased (p = 0). At the end of the intervention period, a significant increase was observed in the hemoglobin, ANC, and platelet counts (p = 0). Fewer patients developed FN while taking honey (p = 0.00004); however, no differences existed between periods in measures of FN, such as duration of FN or hospitalization. Of the patients, 22.7% developed undesirable effects of abdominal pain, vomiting, or diarrhea after taking the honey, and three patients stopped the intervention because of these effects.

The ingestion of honey may have beneficial effects among children with ALL to reduce the incidence of FN, and may have positive effects on hemoglobin and platelet counts.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• The definition of FN is not provided.
• The prevalence of FN was high in this study compared to some other published results from higher income countries; therefore, the findings may not be applicable in higher socioeconomic groups.  
• The duration of any effects of honey ingestion are unknown, so there is no way to know if there were carry-over effects in the crossover design.

Honey ingestion may be helpful in reducing the frequency of FN among patients with ALL. The mechanism of effect is unclear. Hypotheses suggest that honey's effects on FN may be related to its antimicrobial, antioxidant, and immunomudulator properties.

To determine the effectiveness of foot massage on postoperative pain and vital signs for patients with breast cancer in a surgical setting

This study used a quasi-experimental design to investigate the effectiveness of foot massage on postoperative pain and vital signs. The research was conducted in 60 patients following breast surgery. Thirty patients were placed in the control arm, and 30 patients were placed in the experimental arm of the study. The experimental patients received foot massages and analgesics as needed. The control group only received analgesics. All participants filled out a questionnaire to collect demographic data and their non-steroidal anti-inflammatory drug (NSAID) use. Pain levels were assessed using the Visual Analog Scale at a baseline, after 60 minutes, and 120 minutes following the foot massage. Vital signs were taken at the same intervals. The foot massages were done for 20 minutes.

• N = 60  
• AGE = Aged greater than 20 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer surgery; either simple mastectomy or modified radical mastectomy
• OTHER KEY SAMPLE CHARACTERISTICS: Pain level of four or higher

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: National Cancer Institute at the Cairo University Hospital

• PHASE OF CARE: Transition phase after active treatment

Quasi-experimental design with a nonrandom control comparison

• A structured questionnaire was designed by the researchers who collected data about patients' age, level of education, type of surgery, and NSAID use.
• Pain was assessed using the Visual Analog Scale (VAS).
• Vital signs were measured using a deluxe mercurial sphygmomanometer while the patient was lying supine in bed.
• Pulses were measured by counting radial artery beats, and respirations were measured by counting chest movement for a full minute.

There were no statistically significant differences between the two groups regarding age, level of education, use of analgesics, or type of surgery. There was a statistically significant difference on the VAS after one hour in both groups (p ≤ 0.05). There was reduction in pain levels for both groups at one and two hours after analgesic administration and treatment. The mean pain intensity level in both groups decreased at all measurements, but the experimental group's reduction had a higher statistical significance (p ≤ 0.001). Vital signs over time in both groups saw a statistically significant reduction of systolic and diastolic pressure. There was a higher reduction in the experimental group (p ≤ 0.001; f = 53.369 versus f = 32.112; p ≤ 0.001, respectively). There was no significant difference in either group in regard to respirations (p ≤ 0.007).

In this study, foot massages were associated with a greater reduction in pain. The strength of these findings was limited by the study's design.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results

This study identifies a nursing intervention that may help postoperative pain and decrease blood pressure. The intervention was easy, cost effective, and time efficient. Teaching nurses or other healthcare providers would be easy and would allow for the standardization of care. The treatment would be comforting to most patients with very little risk. Nurses need to be aware of patient conditions that would not allow for foot or leg massage. Additional research needs to be done in other patient populations to make the results more generalized. These results point to new areas of research including the relationship between massage and stress reduction.

STUDY PURPOSE: To conduct a meta-analysis comparing the effectiveness of NK₁ inhibitors in preventing chemotherapy-induced nausea and vomiting (CINV) attributed to highly emetogenic chemotherapy (HEC)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 19
• TOTAL PATIENTS INCLUDED IN REVIEW = 6,788
• SAMPLE RANGE ACROSS STUDIES: 16–359
• KEY SAMPLE CHARACTERISTICS: Receiving highly emetogenic chemotherapy (HEC)

PHASE OF CARE: Active antitumor treatment

Antiemetic regimens including an NK₁ inhibitor (aprepitant, fosaprepitant, rolapitant, casopitant, netupitant) prevent CINV attributed to HEC significantly more than antiemetic regimens that do not include it.

Antiemetic regimens containing an NK₁ inhibitor prevent CINV attributed to HEC better than regimens that do not contain it.

Antiemetic regimens should include an NK₁ inhibitor to maximally prevent CINV.

STUDY PURPOSE: To provide a detailed assessment of the efficacy and toxicity of regimens based on rolapitant in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 4 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,856
• SAMPLE RANGE ACROSS STUDIES: 454–1,332 patients
• KEY SAMPLE CHARACTERISTICS: Three studies included patients taking highly emetogenic chemotherapy, one study included patients administered moderately emetogenic chemotherapy. Patients ethnicities are unknown.

PHASE OF CARE: Active antitumor treatment

The pooled RR for the complete response (CR) was 1.23 (95% CI [1.18, 1.33], p < 0.00001) in the overall phase, 1.12 (95% CI [1.02, 1.24], p = 0.02) in the acute phase, and 1.19 (95% CI [1.13, 1.26], p < 0.00001) in the delayed phase. The pooled RR for no significant nausea in the overall phase was 1.17 (95% CI [1.04, 1.32], p = 0.008), and the pooled RR for no emesis in the overall phase was 1.24 (95% CI [1.18, 1.31], p < 0.00001). The efficacy analyses demonstated that rolapitant-based regimens are associated with higher rates of CR (both in overall, acute, and delayed phases). No significant nausea was present and no emesis was present compared with control regimens in highly and moderately emetogenic chemotherapy. The pooled RR of all grade constipation was 1 (95% CI [0.55, 1.82], p = 0.61), and the pooled RR of all grade headache was 1.05 (95% CI [0.57, 1.96], p = 0.87). Therefore, rolapitant-based regimens are not associated with an increased RR for constipation or headache compared with antiemetic control regimens.

This analysis demonstrated that rolapitant-based regimens are associated with higher rates of CR, no significant nausea, and no emesis compared with control regimens in highly and moderately emetogenic chemotherapy. In addition, no increased risk of toxicity with constipation or headache exists when compared with standard antiemetic control regimens. The authors concluded that rolapitant is a valid addition to other available standard antiemetic regimens for highly and moderately antiemetic chemotherapy.

• Limited number of studies included
• Low sample sizes
• Limited information on patient age, sex, diagnosis, and treatment regimens

Rolapitant is associated with higher CR rates, no significant nausea, and no emesis compared to other control regimens in highly and moderately emetogenic chemotherapy without increased toxicity. Rolapitant should be a recommended addition to control regimens that do not include a neurokinin inhibitor.

To assess the efficacy of available strategies to reduce the risk and severity of leg lymphedema

Databases searched were MEDLINE (from January 1966 to April 2009), EMBASE (from January 1980 to April 2009), and the Cochrane Colorectal Cancer Group Specialized Register (January 2009).

Search keywords were inguinal node dissection, lymphedema, malignant melanoma, squamous cell carcinoma, saphenous vein, prevention, and combinations of these words.

Studies were included in the review if they

• Evaluated patients who underwent inguinal node dissection for metastatic malignant disease from the genitalia, lower trunk, or lower limbs.
• Used a comparison group (control) derived from the same population of patients who suffered the same condition.
• Included a cohort of patients with matching demographics, gender, comorbidities, and other forms of treatment, such as radiation therapy.
• Used the same surgical technique for prevention of lymphedema and other complications.
• Included a sufficient follow-up period to evaluate the development of chronic complications.
• Lymphedema has been defined clearly based on limb girth measurements.

The authors did not list the exclusion criteria. However, in the results section, the authors mentioned that two studies were excluded from the meta-analysis because they did not focus on the effect of saphenous vein preservation.

Suitable studies were assessed using the Newcastle-Ottawa scale for evaluation of the quality of nonrandomized cohort studies. This scale uses a star system for evaluation of nonrandomized studies. The grading is based on three criteria: patient selection, comparability of study groups, and outcome assessment. The analysis included studies that scored 6 stars or higher and were considered suitable for inclusion in the meta-analysis. The total number of studies initially reviewed was 14. Of these, 12 were included in the report and 4 in the meta-analysis.

Meta-analysis was conducted with the studies that reported on saphenous vein preservation. The rest were individual reports and were not pooled. The primary outcome was the rates of leg lymphedema. Other outcomes, such as cellulitis, flap necrosis, lymphocele, the number of harvested nodes, and rate of cancer recurrence, were considered secondary endpoints. Studies deemed suitable according to the Newcastle-Ottawa scale were pooled, and the data was entered in ‘‘Metaview’’, which is used by the Cochrane methods for systematic reviews. All of the results were analyzed as dichotomous variables. Statistical heterogeneity in the results of the meta-analysis was assessed by graphical presentations of the confidence intervals (CI) on forest plots and by performing a χ2 test for heterogeneity, in which p = 0.1 was regarded as significant heterogeneity.

Data were analyzed using a random effect model and expressed in odds ratios and a Forest plot. Heterogeneity among the included studies was tested using the Cochrane Q test, with p values < 0.01 to ensure that odd ratios from separate studies were homogenously distributed. A funnel plot then was constructed to visually test for the presence of publication bias.

• The total sample size included in the meta-analysis was 262.
• Sample ranges across all studies in the meta-analysis was 10–139.
• Sample characteristics of the studies in the meta-analysis were patients with vulval malignancies, inguinal lymphadenectomy, and saphenous vein preserved or sacrificed.

The search result defined few studies that reported results of saphenous vein sparing technique; some of those studies were found suitable for meta-analysis based on the Newcastle-Ottawa scale for nonrandomized studies. The meta-analysis showed significant reduction of lymphedema (odds ratio 0.24; 95% CI, 0.11–0.53) and other complications of inguinal node dissection. No randomized studies addressed this problem. Isolated studies reported on the benefits of other techniques, but none of them was suitable for meta-analysis.

Meta-analysis of the reported studies on sparing the long saphenous vein in inguinal node dissection suggests a reduced rate of lymphedema and other postoperative complications.

Other methods that may be beneficial are fascia preserving dissection, pedicledomental flap, and microsurgery. Sartorius transposition has not been shown to reduce the rate of complications. Randomized controlled trials are needed to prove the benefits of various technical modifications.

To evaluate whether neutropenia prophylaxis could be limited to the first two cycles of chemotherapy only, based on the observation that patient risk for febrile neutropenia (FN) is highest in the first two cycles

Patients receiving chemotherapy every three weeks with regimens associated with more than a 20% risk of FN were randomly assigned to receive a granulocyte–colony-stimulating factor (G-CSF) throughout all chemotherapy cycles (standard arm) or during the first two cycles only. Pegfilgrastim (6 mg) was given 24–30 hours after chemotherapy administration. Participating sites were stratified according to whether they used prophylactic antibiotics.

• N = 167   
• MEDIAN AGE = 50 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had breast cancer. The majority were receiving TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Netherlands

• PHASE OF CARE: Active antitumor treatment

• Randomized, parallel-group, noninferiority trial

• Blood cell counts

The incidence of FN was 10% with standard treatment and 36% in the experimental arm. Grade 3–4 neutropenia occurred in 6% of the standard arm versus 51% of the experimental arm, and confirmed infection occurred more often in the experimental arm. The study was closed prematurely because of an unacceptablely high rate of FN.

The findings showed that the incidence of FN was higher among patients who did not receive G-CSF during each cycle of chemotherapy.

• Risk of bias (no blinding)

The findings showed that patients who did not receive recommended CSF prophylaxis during each cycle of chemotherapy had significantly higher rates of FN. These results showed that the provision of prophylaxis according to recommended guidelines is important for FN prevention.

To compare the efficacy and safety of netupitant plus palonosetron (NEPA) compared to palonosetron alone in preventing chemotherapy-induced nausea and vomiting (CINV)

Chemotherapy-naïve patients receiving anthracycline- or cyclophosphamide-based chemotherapy were randomized to receive a single dose of PO NEPA (300 mg netupitant plus 0.50 mg palonosetron) and 12 mg dexamethasone or a single dose of 0.5 mg PO palonosetron and 20 mg dexamethasone on day 1, cycle 1, of their chemotherapy. Delayed (25-120 hours post chemotherapy) CINV was evaluated as the primary end point.

• N = 1,455 (participated in a total of 5,969 chemotherapy cycle extension)   
• MEDIAN AGE = 54 years
• MALES: 2%, FEMALES: 98%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Solid tumor cancer, 98% with breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Aged older than 18 years; chemotherapy-naïve; anthracycline- or cyclophosphamide-based chemotherapy; European Cooperative Oncology Group (ECOG) score of 0, 1, or 2; not receiving prolonged chemotherapy from day 1-5; not receiving abdominal radiotherapy; no bone marrow transplantation; did not received any antiemetics 24 hours before chemotherapy and did not experience anticipatory nausea and vomiting

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Multinational

PHASE OF CARE: Active antitumor treatment

Double-blind, randomized

• Diary: Emesis episodes and rescue medications used from 0-120 hour each cycle
• Visual analog scale (VAS) for nausea from 0 (no nausea) to 100 (nausea as bad as it could be)
• Proportion of patients with complete response (0-120 hours)
• Review treatment emergent adverse effects, ECG, troponin levels

Participants who received NEPA and dexamethasone reported complete remission (no emesis or rescue antiemetics) significantly more than participants who received palonosetron and dexamethasone (p ≤ 0.001).

NEPA and dexamethasone may offer more control over CINV compared to palonosetron and dexamethasone.

• Measurement validity/reliability questionable
• Using VAS for nausea and vomiting

Combination antiemetic therapies have been shown to provide more relief from CINV compared to single agents. The results of this study demonstrated that NEPA given with dexamethasone did prevent CINV better than palonosetron and dexamethasone.

To compare two treatments (palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3) for the management of chemotherapy-induced nausea and vomiting (CINV) in the overall study period (days 1–5) and to show comparison between the two treatments in complete response (CR) rates

• At the first cycle of chemotherapy, patients were randomly assigned to receive one of two treatment regimens. Group one received 0.25 mg palonosetron plus 8 mg IV dexamethasone on day 1 and placebo on days 2 and 3, and group two received 0.25 mg palonosetron plus 8 mg dexamethasone on day 1 and 4 mg oral dexamethasone twice a day on days 2 and 3.
• Patients recorded emetic episodes, use of rescue medication, and daily nausea ratings of nausea in diaries.
• Patients were allowed to take rescue medication, and the choice of rescue medication was at the discretion of the individual physician, except that no phenothiazines were allowed.

• The study consisted of 300 participants.
• Mean age was 51.6 years old (SD = 10.11 years).
• The sample was 100% female.
• Participants were chemotherapy-naïve patients with breast cancer receiving moderately emetogenic chemotherapy (MEC).

The study was conducted at multiple outpatient settings in Austria, Germany, Italy, and Spain.

This was a double-blind, randomized, controlled study.

• Patients used diaries to record date and time of emetic episodes, use of rescue medication, daily nausea ratings on a 0-10 visual analogue scale (VAS). 
• CR rate, defined as no emesis and no rescue medication during overall period (days 1–5), was recorded for acute phase (day 1) and delayed periods (days 2–5).
• Maximum severity of nausea (MSN) was recorded in daily and overall phases.
• Time-to-treatment failure (time to first emetic episode or time to first use of rescue medication) was recorded.
• Functional Living Index—Emesis (FLIE) was used in the screening phase and on day 6.
• Adverse events were recorded.

• More than 70% of patients had no emesis.
• CR was not significantly different in the overall, acute, and delayed phases between study groups. However on day 3, patients who received palonosetron plus dexamethasone on days 1–3 experienced less emesis (p = 0.004) and lower MSN (p = 0.028).
• Time-to-treatment failure and use of rescue medication was similar between groups.
• FLIE score and percentage of adverse events was not significantly different between groups.

• The palonosetron with single-day dexamethasone dosing regimen offered high and similar protection as palonosetron with 3-day dosing of dexamethasone in terms of CR rates and patient performance.
• In some cases, the protection was insufficient on day 3, and the benefits of dexamethasone needed to be weighed against the increased risk of potential side effects.

• The sample was only women who were chemotherapy naïve receiving MEC regimens. These findings may not be generalizable to other groups, particularly as some research has shown differences in antiemetic results between men and women.
• Patient compliance with daily diary recordings was not discussed.

• With chemotherapy-naïve patients with breast cancer receiving chemotherapy, palonosetron plus dexamethasone provides fairly good control over CINV.
• In patients whose antiemetic-related side effects have been bothersome, a palonosetron plus single-dose dexamethasone regimen could be an option.
• In both groups, more than half of patients still had nausea on day 1 and about one-third still had nausea in the delayed period, pointing to the need for individualization of ongoing management.

To determine if the granulocyte–colony-stimulating factor (G-CSF) biosimilar filgrastim had similar outcomes for adults and older adult patients actively undergoing treatment for cancer

This was a prospective observational study of patients prescribed biosimilar filgrastim in 140 centers in 12 European countries.

• N = 1,447 patients; 41% were older than age 65 years (cut-off at age 65 years) and put into the older adult category   
• AGE = Adults aged 18 years or older
• MALES: 49.8% older adult, 31% adult
• FEMALES: 50.2% older adult, 69% adult
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Stage III–IV breast, ovarian, bladder, and lung cancer; metastatic prostate cancer as well as stage III–IV large B-cell lymphoma and multiple myeloma

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: 12 European countries

• PHASE OF CARE:  Active antitumor treatment
• APPLICATIONS: Elder care

Prospective observational

Comparative analysis of various components outlined by the authors

No statistically significant differences existed in the rates of chemotherapy-induced neutropenia and febrile neutropenia episodes between either groups. G-CSF support is equally important in both groups. Older adult patients with underlying chronic conditions may be at higher risk for febrile neutropenia; in both groups, it is important to provide timely prophylaxis.

Timely G-CSF support is important in both older adult and adult patients receiving myelotoxic chemotherapy.

Nurses need to be aware of G-CSF administration for patients after chemotherapy. Independent of age group, it is important that patients receiving specific regimens get timely G-CSF treatment to prevent neutropenia duration.

The purpose of this article was to update existing guidelines for prophylactic granulocytye–colony-stimulating factor (G-CSF). The article focuses on patients receiving chemotherapy, not limited to one definition of febrile neutropenia (FN). No studies with pediatric patients or patients with leukemia were included.

This guideline resource used a process where articles were rated using the table listing below.

Level                Type of Evidence
A                        Evidence of type I or consistent findings from multiple studies of types II, III, or IV
B                       Evidence of types Ii, II, or IV and findings are generally consistent
C                       Evidence of types Ii, II, or IV, but findings are inconsistent
D                       Little or no systematic empirical evidence 

Information from papers included in meta-analyses were only used to answer questions not included in the meta-analyses. Publications available from Congress presentations previously included as abstracts were only used is they provided answers not yet presented. Authors were contacted if their abstracts were relevant and publications noted as missing or “in press” were included.

Regarding a search strategy, the MEDLINE, PreMEDLINE, EMBASE, and Cochrane Library databases were used.

Key words included antineoplastic agents, filgrastim, granulocyte–colony-stimulating factor, lenograstim, neoplasms, neutropenia, pegfilgrastim, and guideline

Articles were included if they were recent reviews, any primary papers deemed relevant, and meta-analyses subject to manual review. In addition to filgrastim and pegfilgrastim, two filgrastim biosimilar molicules, XMO2 and EP2006, daily G-CSFs have been approved in Europe. 

Articles were excluded if their studies included patients younger than age 18 years or patients with a diagnosis of leukemia.
 

• The phase of care is active chemotherapy treatment
• Applications is adult patients receiving chemotherapy.
   

Recommendations  Primary prophylactic G-CSF is recommended for patients at risk and should be started 24–72 hours following completion of the first cycle.

Step I:

• Assess frequency of FN associated with planned chemotherapy regimen, and reassess with each cycle.
• If FN risk is less than10%, G-CSF prophylaxis is not recommended. If FN risk is greater than 20%, prophylactic G-CSF is recommended.
• If FN risk 10%–20%,  proceed to step 2.

Step 2: 

• Assess for high risk: age older than 65 years.  
• Increased risk (level I, II evidence): Advanced disease, history of prior FN, no antibiotic prophylaxis, no G-CSF use
• Other factors (level III, IV evidence): Poor performance/nutritional status, female, Hgb < 12 g/dl, liver, renal, cardiovascular disease
• and then proceed to step 3

Step 3: 

• Define the patient’s overall FN risk for planned chemotherapy regimen.
• If overall FN risk is greater than 20%
• Secondary prophylaxis: Start G-CSF if neutropenic event occurred in previous cycle.

Provides percent risk for development of FN for some tumor types based on chemotherapy regimen. Identifies additional risk factors, but provides little guidance on how to use these to calculate an increase in risk that would warrant prophylactic G-CSF.
 

The article included results from an updated literature search to identify patient and chemotherapy regimen risk factors for developing FN, use of prophylactic G-CSF, G-CSF with existing FN, impact of overall FN risk on G-CSF use, and choice of G-CSF formulation. It was difficult to identify new information as recommendations were combined with existing recommendations.