The objective of the study is to compare the symptomatic effectiveness of palliative oxygen against room air in providing relief for patients with life-limiting illness, refractory breathlessness, and PaO₂ greater than 7.3 kPa (54.75 mmHg).

Eligible participants underwent arterial blood gas assessment in an outpatient clinic or at home. Those with PaO₂ greater than 7.3 kPa were assigned in a 1:1 ratio to receive oxygen or room air delivery by a concentrator and nasal cannula. Medical gas was administered continuously at 2 liters per minute via nasal cannula, and participants were instructed to use concentrators for at least 15 hours per day and record the amount of “breathlessness right now” twice a day (within 30 minutes of waking up in the morning and going to bed in the evening). Diaries also captured secondary outcomes, including average dyspnea in the previous 24 hours, worst breathlessness in the previous 24 hours, relief of dyspnea during the previous 24 hours, and ordered categorical scales for functional impact, sleep disturbance, drowsiness, anxiety, nasal irritation, and nose bleeds. Quality of life also was assessed every day, as well as functional changes .

The study reported on a sample of 239 patients; 120 were in the oxygen group, 119 were in the room air group, and 13 withdrew from the study before it started and any data were collected.

The sample was 62% male and 38% female.

Key disease characteristics were chronic obstructive pulmonary disease (COPD) (152), restrictive lung disease (14), bronchiectasis (7), primary pulmonary hypertension (3), primary lung cancer (33), known secondary lung cancer (5), pleural effusion (2), end-stage cardiomyopathy (7), and other (16).

Patients were excluded if they met international eligibility guidelines for long-term oxygen therapy, had a history of hypercarbic respiratory failure with oxygen, had anemia (Hgb less than 100 g/L ), were hypercarbic, or had cognitive impairment.

The median age for the oxygen group was 73 years, and the median age for the room air group was 74 years.
 

The study was conducted in a multi-site, outpatient setting at outpatient pulmonary, palliative care, oncology, and primary clinics at five sites in Australia, two sites in the United States, and two sites in the United Kingdom.

• Patients were undergoing end-of-life care.
• The study has clinical applicability for end-of-life and palliative care.
   

The study was a double-blinded, randomized, controlled trial.

• Folstein mini-mental status examination score to assess for cognitive impairment during screening process, prior to study commencement
• Eastern Cooperative Oncology Group (ECOG) performance status scale
• Numerical Rating scale (NRS) from 0-10 adjusted with 1-point reduction in self-reported dyspnea
• McGill Quality of Life Questionnaire (MQoLQ)
• Participant diary entries capturing secondary outcomes (average dyspnea in the previous 24 hours, worst breathlessness in the previous 24 hours, relief of dyspnea during the previous 24 hours, sleep disturbance, drowsiness, anxiety, nasal irritation, and nosebleeds) using ordered categorical scales
• Medical Research Council (MRC) 4-point categorical dyspnea functional scale to assess functional changes and a 4-point categorical dyspnea exertion scale measured daily
• 5-point Likert-type categorical scale to measure side-effects
   

Thirteen patients (5%) withdrew before the study started, and no assessments were completed. Fifteen patients (6%) withdrew before the day six assessment and completed data. Longitudinal analyses measuring the clinical effect of the interventions found significant improvement in morning and evening dyspnea in both oxygen and room air groups (time p < 0.0001), but the primary outcome of breathlessness did not differ between groups at any time during the study period. Quality-of-life measures were similar between groups. Reports of participants’ worst level of functioning on the MRC dyspnea scale and sleep disruption from breathlessness decreased during the seven-day study with little difference between groups. Baseline dyspnea also seemed to predict evening response, regardless of intervention.

Based on study results, palliative oxygen does not provide benefit over room air for relief of breathlessness in patients who were not hypercarbic.

Exact times of morning and evening assessments and times during which participants used prescribed gases were not recorded. Due to the heterogeneous nature of the patient population, assessing which patient subgroup (e.g., patients with COPD versus patients with cancer) may have experienced better symptomatic relief from palliative oxygen is difficult. Because most participants had an ECOG performance status of 2 or 3 with no breathlessness at rest, the patient population may not be representative of the sickest patients in palliative care who would frequently receive palliative oxygen. Also, more randomized participants withdrew from the room air group than the oxygen group, causing potentially skewed results. The authors also question the clinical significance of demonstrated benefit, when considering their means of defining symptomatic relief (i.e., NRS with 1-point change), and note the possibility that secondary analyses might be underpowered. Similarly, objective measures of dyspnea (oxygen saturation, hemodynamics, and sleep) had not been recorded for comparison to subjective results of the study. Gauging participant compliance with instructed use of interventions for the prescribed 15 hours per day also was difficult. While authors note a slightly lower usage (14 hours per day), most responses occurred within the first 24 hours, and they note the unlikelihood that stricter adherence would change outcomes. Finally, regardless of baseline NRS, all participants were relegated to 2 liters per minute of either oxygen or room air by nasal cannula, thus calling into consideration the benefits of titrating oxygen to higher delivery levels. 

Prescription of palliative oxygen therapy may not be a cost-effective and scientifically based clinical intervention for the relief of breathlessness. Oxygen is expensive, flammable, and should be monitored carefully when prescribed for patients with potentially hypercarbic states and central hypoventilation syndromes.

To evaluate the effects of ​goshajinkigan (GJG) compared to vitamin B12 on the incidence of docetaxel (DOC)-associated peripheral neuropathy (PN) in chemotherapy-naïve patients with breast cancer

Patients were stratified by type of chemotherapy and age for randomization by dynamic allocation (balanced marginal distribution of stratification factors) then randomly assigned to receive either GJG (7.5 g per day orally divided into two to three doses before or between meals during DOC therapy) or B12 (1,500 mcg per day orally after meals daily during DOC therapy). A baseline evaluation of adverse effects was completed on days 1 and 8 by nurses. using the Neurotoxicity Criteria of Debiopharm (DEB-NTC), the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), and a Visual Analog Scale (VAS) for pain. The VAS for pain was completed again after DOC chemotherapy. The study continued as long as DOC treatment or for six cycles. Patients were premedicated with 5-HT receptor antagonists and corticosteroids. A granulocyte-colony stimulating factor (filgrastim or lenograstim) was administered if a patient's neutrophil was less than 500/mcL or if febrile neutropenia occurred. Chemotherapy regimens included TC (DOC 75 mg/m² and cyclophosphamide 600 mg/m² for three weeks for four cycles), single-agent DOC (DOC 100 mg/m² for three weeks for four cycles), and XT (capecitabine 900 mg/m² PO BID on days 1–14 and DOC 60 mg/m² for three weeks for six cycles). Patients receiving HER-2 therapy received trastuzumab before chemotherapy.

• N = 57
• MEDIAN AGE = 58 years (range = 33–70 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer stages I, IIa, IIb, and III

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: Shiga University of Medical Science Hospital, Shiga, Japan

• PHASE OF CARE: Active antitumor treatment

Prospective, randomized, parallel-group trial

• Neurotoxicity Criteria of Debiopharm (DEB-NTC)
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE v3.0)
• Visual Analog Scale (VAS) for pain

The incidence of PN was significantly lower in the group receiving GJG (39.3%) compared to the group receiving B12 (88.9% [p < 0.01]). The incidence of grades 2 and 3 PN were significantly lower in the group receiving GJG compared to the group receiving B12 (DEB-NTC = p < 0.01 and NCI-CTCAE p < 0.01). The mean VAS score was significantly lower in the group receiving GJG (2.7 + 2.2) versus B12 (4.9 + 2.4 [p = < 0.01]). There were no significant differences in characteristics between the groups. The completion rate and recommended dietary intake percent were similar for the GJG and B12 treatment groups. The total dose of DOC was 338.5 mg/m² in the GJG group versus 340 mg/m² in the B12 group.

The findings of this study suggest that GJG might be helpful in the prevention of PN in patients receiving chemotherapy regimens that include DOC. However, additional research to develop strong evidence in this area is needed.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Findings not generalizable
• Other limitations/explanation: There was a reporting discrepancy in which N = 57 patients enrolled in results, but the data report n = 33 in the GJG group and n= 27 in the B12 group, totaling 60 patients. There is no explanation for drop-outs or missing data. There was no placebo control group receiving only chemotherapy. There was no explanation of the study's timeframe. The VAS was completed at baseline and after DOC chemotherapy, but the methods of assessment not well described. The study included conflicting reports of patient characteristics, stating that 16% of patients received neoadjuvant chemotherapy even though this was stated as an exclusion criterion. It was unclear whether the total DOC dose between groups was significant. It was reported that there was no difference between groups regarding other toxicities, but the data displayed frequencies not of significance with the chi square P value. There was no report regarding the timeframe of PN onset or occurrences during treatment between groups. The use of B12 was reported as increasing the incidence of neurotoxicity, yet no control group existed as a frame of reference to make this assumption. A break-down of the data differences in the PN scales used (NCI-CTCAE and DEB-NTC, sensory severity/impairment and duration) was not provided. The definitions of grades are different between the two scales.

GJG at 7.5 g per day orally divided into two to three doses before or between meals may be beneficial to reduce incidence and severity of PN in patients with breast cancer receiving first-time DOC regimens. The safety and efficacy of this treatment need to be validated in larger randomized, controlled trials that compare GJC to placebos and use other assessment instruments.

To investigate the effects of olanzapine as an adjunct to triplet antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy

All patients in the trial were receiving triplet therapy in accordance with Japanese guidelines and 5 mg olanzapine one day prior to cisplatin administration then once daily on days 1–5 at bedtime. Metoclopramide was used as rescue therapy for breakthrough emesis. Patients were hospitalized during treatment.

• N = 40
• MEDIAN AGE = 57 years (range 25–76 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had cervical, endometrial, or vulval cancer at varied stages. 50% experienced emesis during pregnancy, and 32.5% had a history of motion sickness. Most received cisplatin at a dose of 50mg/m² and 95% had multiagent regimens.

• SITE: Multi-site  
• SETTING TYPE: Inpatient    
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Prospective trial

• Patient diary for daily self-reported symptoms
• Eleven-point Numeric Rating Scale (NRS) for nausea
• Complete response defined as no vomiting, no rescue therapy and no significant nausea
• Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

There were no grade 3 or 4 adverse events. In the overall phase (acute and delayed phases), the complete response rate was 92.5% with 97.5% in the acute phase and 95% in the delayed phase. The rate for no nausea was 87.5% in the acute phase and 67.5% in the delayed phase. The authors provided a comparison of this study's results with those of a collaborative group trial using triplet therapy. This comparison showed that the addition of olanzapine was associated with better response rates across all phases and higher rates of nausea control. The adverse effects reported were low-grade and included constipation, dry mouth, and dizziness.

The addition of olanzapine to triplet antiemetic therapy in patients receiving highly emetogenic chemotherapy was associated with high rates of complete CINV control across all phases and relatively low rates of nausea during the acute phase.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: The results were complete control and no significant nausea, but these were not defined and the level of no significant nausea was not clear. The way in which the numeric scale data were used was not clear (i.e., was this the average, worst, or least scores recorded by the patient).

Triplet drug therapy to prevent CINV is recommended and is effective with highly emetogenic chemotherapy. However, even with this approach, the control and prevention of nausea is challenging. The findings of this study suggest the addition of olanzapine to triplet therapy may improve nausea control and overall CINV prevention with no severe adverse effects. This study has several limitations, but provides promising results. Additional, well-designed research testing the impact of olanzapine for CINV prevention is warranted.

To evaluate the effect of topical use of honey and a mixture of honey, olive oil-propolis extract, and beeswax (HOPE) as natural products in the treatment of chemotherapy-related oral mucositis

Patients were randomly assigned to one of three groups, with 30 patients in each group. All patients used routine oral care, which included toothbrushing with a soft brush and normal saline rinses three times daily before topical treatment. All treatments were done three times daily to affected oral mucosa until healing or for 10 days, whichever came first. Topical treatments in each group were performed by the resident or nursing staff under researcher supervision.    

• Group 1 (Honey group) applied 0.5 g honey/kg (maximum 15 g) topically to affected oral mucosa.            
• Group 2 (HOPE group) used 0.25 g/kg (maximum 5 g) of a 4:2:1 mixture of honey, olive oil-propolis extract, and beeswax.                                                                 
• Group 3 (control group) received benzocaine 7.5% gel.

• The group consisted of 90 patients, ranging in age from 2–18 years old.
• Mean patient age was 6.9 years. Mean patient age was 9 years (SD = 3.8 years).
• The sample was 63% male and 37% female.
• Patients were included in the study if they
  • Had an acute lymphoblastic leukemia (ALL) diagnosis.
  • Were undergoing the consolidation phase of treatment with methotrexate.
  • Had chemotherapy-related oral mucositis grades 2 and 3 based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
• Patients were excluded if they
  • Were diagnosed with diabetes mellitus.
  • Had received antiviral/antifungal therapy or any other treatment for oral mucositis before enrollment.
  • Were experiencing neutropenia with absolute neutrophil count (ANC) of more than 1,500.
  • Had advanced or severe periodontitis (periodontal pockets of 6 mm or greater).

The study was conducted at a single site, inpatient setting at Hematology-Oncology of Children's Hospital of Ain Shams University in Egypt.

• Patients were undergoing the active treatment phase of care.
• This study has clinical applicability for pediatrics.

This was a randomized, non-blinded, controlled, clinical phase II trial.

• The primary outcome measure was recovery time, defined as number of days from initiation of treatment to when complete healing of all ulcers occurred.    
• The NCI-CTC was used.

• In patients with grade 2 mucositis, recovery time was reduced in the honey group as compared with either the HOPE or control groups (p < 0.05).
• In patients with grade 3 mucositis, recovery time did not differ significantly between honey and HOPE (p = 0.6).
• Compared to controls, both the honey and HOPE groups had significantly faster healing (p < 0.01).
• Comparing both grades, honey produced faster healing as compared with either control (p = 0.005; statistical power of 96.2%) or HOPE (p = 0.0056; statistical power of 81.9%).

The superiority of topical honey alone may be related to the amount of honey used as well as better distribution in the oral cavity.

• The sample size was small with fewer than 100 patients.
• The study was not blinded to both researcher and patient.
• The study only involved a select group (pediatrics).
• The authors have a pending patent application for the mixture of honey, beeswax, and olive oil-propolis extract.
• No description was provided regarding the management of mucositis in the control group.
• No information was provided about other treatments for mucositis-related pain.

Mucositis is a significant debilitating side effect of cancer therapy. Effective interventions to reduce or eliminate the severity of this symptom are needed. Further research is needed in all patient populations.

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.