Fourteen allogeneic patients with 15 episodes of diffuse alveolar hemorrhage (DAH) were treated with Solu-Medrol^®; eight of these patients also received aminocaproic acid 1,000 mg IV every six hours.
 

• MEDIAN AGE = 41 years
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who have undergone allogeneic hematopoietic stem cell transplantation; time to DAH from transplant was 40.5 days (range: 11–177 days); failure to improve was the most common reason for adding aminocaproic acid.
   

• Retrospective study

• 100-day mortality
• Median transplant survival
   

Overall 100-day survival was 60%, and the median transplantation survival was 99 days. Patients treated with aminocaproic acid improved to a 100-day mortality of 44% and 167-day median transplant survival, compared to those not treated with aminocaproic acid with an 83% 100-day mortality and 96.5-day median transplant survival.

• Respiratory failure cause of death in 89%
• Median coagulation parameters were near normal; range with no difference in the two groups
• Small sample size
• Retrospective in nature
   

To determine the effect of postoperative intravenous sufentanil for patient-controlled analgesia (PCA) use combined with music therapy on pain and hemodynamics in patients with lung cancer after surgery

Before operation, a music therapist guided patient to hypnosis with music-assisted progressive muscle relation. During the operation, the music intervention was suspended. At three, seven, 15, and 19 hours after the operation, the music intervention was implemented in one-hour sessions in the intensive care unit.

• N = 60  
• AVERAGE AGE = 53.8 years (SD = 11.2 years) control; 53.5 years (SD = 10.7 years) music
• MALES: 58%, FEMALES: 42%
• KEY DISEASE CHARACTERISTICS: Patients with stages 1 and 2 lung cancer receiving resection
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria included opioid allergies, blood coagulation dysfunction, asthma, peptic ulcers, liver and kidney disease, hearing impairments, alcohol or drug abuse, mental illness or memory dysfunction, inability to operate PCA, and professional music background.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Intensive care units

• PHASE OF CARE: Multiple phases of care

Randomized, controlled, single-blinded trial

• Self-Rating Anxiety Scale (SAS)
• Visual Analog Scale (VAS)
• Hemodynamic measurements included systolic blood pressure, diastolic blood pressure, heart rate, arterial oxygen saturation, and respiratory rate.
• Sufentanil consumption and adverse reactions

Participants in the music therapy group had significantly lower VAS scores, blood pressure, heart rate, SAS scores, postoperative analgesic use, and sufentanil doses within 24 hours after surgery when compared to the control group.

Intravenous sufentanil PCA combined with music therapy improved PCA use after lung cancer surgery. Lower doses of sufentanil and less frequent PCA use were reported. In addition, combined therapy reduced blood pressure and heart rate.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement validity/reliability questionable

This study suggested that combined music and sufentanil therapy can effectively improve PCA effects and reduce the dose of sufentanil needed while decreasing the blood pressure and heart rate in patients who received lung cancer resections.

The purpose of this study was to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematologic malignancies.

MEDLINE, EMBASE, the Cochrane-controlled trials register, and the Cochrane Library and Science Citation Index were searched.

Key words included itraconazole, fluconazole, hematologic malignancies, meta-analysis.

Only studies published as an abstract or journal article after 2009 were included. Studies not published as an abstract or in a journal were excluded, as were any studies prior to 2009.

6,574 total reference were retreived. 

Two independent reviewers extracted data and entered that data into a freeware program (Review Manager 5.0). Differences expressed as the risk ratio with 95% confidence interval (CI); heterogeneity was checked by using a Q-test; random effects model was used prior to pooling of data; sensitivity analysis to assess if modification of inclusion criteria affected final result; publication bias was assessed by funnel plots.
 

• After exclusion, 9 studies remained in the total sample. 
• Total amount of subjects was 2,254.
• Size of the sample ranged across studies from 59–581.
• Fluconazole dosing ranged from 100 mg PO daily to 400 mg daily; itraconazole dosing ranged from 2.5 mg/kg every 12 hours to 400 mg per day; no other sample characteristics were given (i.e., age, gender, etc.).

Active treatment

Results suggested that prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in prevention of fungal infections and invasive fungal infections (RR = 1.33, 95% CI [1.02, 1.73], p = 0.03). No differences were noted in overall mortality, fungal-related mortality, or proven fungal infections. Fewer patients on fluconazole were withdrawn from studies due to adverse events (RR = 0.45, 95% CI [0.27, 0.75], p = 0.002).

 As there were no differences in mortality or proven fungal infections, it is unclear what outcome was used that showed a difference in efficacy.

• Heterogeneity is a potential problem
• Dosages and duration of both itraconazole and fluconazole were varied throughout.
• No definitions of outcomes used is provided.

While the results support itraconazole, the medication is associated with higher adverse effects.

STUDY PURPOSE: To review randomized, controlled trials on the current evidence on the therapeutic effects of acupoints stimulation for patients with cancer with anxiety and depression

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 11
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,073
• SAMPLE RANGE ACROSS STUDIES: 30–302
• KEY SAMPLE CHARACTERISTICS: Six studies were of breast cancer; one, lung; one, gynecologic; and three involved more than two types of cancer. Eight had a two-arm design, and three had a three-arm design. All assessed anxiety and/or depression.

APPLICATIONS: Palliative care

Overall, the findings really did not support acupoints as a useful approach for managing anxiety and depression. Although it has limited risks, it may be useful in patients who do not tolerate oral medications. Results should be interpreted with caution because of the limitations identified. Still, much needs to be researched in this area. Study heterogeneity and lack of standardization of care and design are some of the major limitations to this meta-analysis. Further studies including controls for environmental as well as study site differences are needed before these results can be interpreted. Generalizability is not possible outside of the current study demographics, which should also be taken into account for future studies.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity

Acupoints could be a safe intervention used in clinical practice for patients with cancer who experience anxiety and depression. No serious harm was reported, so it could be used as an alternative to medications when patients do not tolerate. Still, much research needs to be conducted in this area.

To compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with curative intent

Seven prophylaxis strategies were evaluated: (a) primary prophylaxis (PP) with biosimilar filgrastim throughout all cycles of chemotherapy, (b) PP with biosimilar filgrastim during the first two cycles of chemotherapy, (c) secondary prophylaxis (SP) with biosimilar filgrastim, (d) PP with pegfilgrastim throughout all cycles of chemotherapy, (e) PP with pegfilgrastim during the first two cycles of chemotherapy, (f) SP with pegfilgrastim, and (g) no prophylaxis (NP). Cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy.

• N = N/A   
• AGE = N/A
• MALES: N/A, FEMALES: N/A
• CURRENT TREATMENT: Chemotherapy, immunotherapy
• KEY DISEASE CHARACTERISTICS: Patients with non-Hodgkin lymphoma (NHL) treated with R-CHOP

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Singapore

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

• Case-controlled study using published data set to estimate the rate of FN
• A mathematical model was used to compare anticipated costs.

A Markov model was constructed with TreeAge Pro 2013 to compare seven prophylaxis strategies for FN. Primary prophylaxis was defined as the routine administration of a granulocyte–colony-stimulating factor (G-CSF) with each cycle of chemotherapy, regardless of whether the patient had previously experienced an episode of FN. Secondary prophylaxis was defined as the initiation of a G-CSF in subsequent cycles of chemotherapy after the patient experienced a FN episode. The model target population was a hypothetical cohort of patients with NHL (mean age = 55 years) undergoing R-CHOP as a curative treatment. The time horizon of this model was 18 weeks, which was the period of six chemotherapy cycles. The Markov model was used with a cycle length of one week (seven days). Data from observational studies were used to determine the anticipated rate of FN.

The costs associated with the strategies were $3,813 (strategy 2), $4,056 (strategy 5), $4,545 (strategy 1), and $5,331 (strategy 4), respectively. The incremental cost-effectiveness ratios were $13,532 for strategy 5 versus strategy 2, $22,565 for strategy 1 versus strategy 5, and $30,452 for strategy 4 versus strategy 1, respectively, per episode of FN avoided. Strategy 2 was the most cost-effective.

The routine use of prophylactic G-CSF in the first two cycles of R-CHOP for NHL was more cost-effective than the routine use of G-CSF for all cycles of chemotherapy, with minimal clinical significance on efficacy. Routine use of prophylactic G-CSF during the first two cycles of R-CHOP for NHL or during all cycles of R-CHOP was more cost-effective than no prophylaxis.

• Risk of bias (no random assignment)
• This study used a mathematical model with data sets to predict the costs associated with G-SCF use.
• The study did not enroll patients to evaluate outcomes.
• The authors assumed that using a biosimilar filgrastim for seven days would have the same outcomes as pegfilgrastim.

Using G-CSF is a cost-effective way to prevent FN in patients undergoing R-CHOP chemotherapy. Cost-effectiveness is further improved when a G-CSF is used during the first two cycles, but this may produce different clinical benefits, requiring further study.

To examine the effects of a multidisciplinary intervention on fatigue

The intervention group received training in individual sessions at week one, three, and six. A physical therapist provided education in deep breathing and designed a program of physical exercises to do at home. A nutritionist assessed needs and educated patients in nutrition during therapy. A nurse met with the patient, providing general psychoeducational intervention. All specialists had sessions with the patient at all study time points.

• N = 60   
• MEAN AGE = 56.1 years
• AGE RANGE: 45–65 years
• MALES: 68.3%, FEMALES: 31.7%
• KEY DISEASE CHARACTERISTICS: Lung cancer, undergoing chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Fatigue, pain, and peripheral neuropathy were the most frequent symptoms at baseline.

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

• PHASE OF CARE: Active antitumor treatment

• RCT

• Piper Fatigue Scale

At the end of the study, the trial group had a lower fatigue score than controls (p = .036).

A multidisciplinary intervention to promote self-care may reduce symptoms of fatigue.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: No information about patients' actual practice of exercise and other recommendations is provided. No baseline fatigue levels are provided.

Education provided by a multidisciplinary group may be beneficial and positively impact fatigue during cancer therapy.

The purpose of the study was to evaluate whether oral glutamine reduced the incidence and severity of peripheral neuropathy in patients receiving oxaliplatin.

A total sample size of 86 patients with colorectal cancer were enrolled. Forty-two patients received glutamine and 44 did not. Patients received oxaliplatin 85 mgm/m², 5-FU  bolus 500 mgm/m², and folinic acid 20 mgm/m². Patients received glutamine 15 g twice a day for seven days every two weeks starting on the day of treatment. Patients were assessed at baseline for neurological toxicity and electrophysiological toxicity and again assessed at cycles 2, 4, and 6.

The 86 patients enrolled in the study had adenocarcinoma of the colon or rectum.

The study took place from September 2004 to December 2005.

The study had a non-randomized, pilot design.

Glutamine supplementation significantly reduced the incidence and severity of oxaliplatin-induced neuropathy. After two cycles of treatment, grade 1–2 sensory neuropathy was significantly lower in the intervention group versus the control group. The percentage of grade 3–4 sensory neuropathy was lower in the glutamine group after four cycles of treatment and remained that way for six cycles. In addition, glutamine supplements lowered peripheral nerve hyperexcitability and interference with activities of daily living. Glutamine supplementation also reduces the need for oxaliplatin dose reduction without affecting response to chemotherapy and survival.

• Concerns exist concerning glutamine supplements possibly protecting tumor cells from the cytotoxic effects of chemotherapy.
• The study was a non-placebo controlled, non-blinded study with a relatively small sample size; therefore, causality cannot be inferred.
• There was no between-group difference detected. 

Glutamine is a potential neuroprotective agent that needs to be studied in larger populations in a randomized, placebo-controlled trial.

To assess the impact of education on analgesic medication for patients with cancer-related pain

Patients were randomly assigned to control or education groups. The education group received three information booklets and eight face-to-face education and counseling sessions over four weeks. Clinical pharmacists contacted patients daily to review outcomes and made recommendations to physicians based on patient response.   Pharmacists received standardized training. Pharmacists assisted patients to complete study questionnaires.

• N = 237  
• MEAN AGE = 51.3 years
• AGE RANGE = 23–70 years
• MALES: 79%, FEMALES: 21%
• KEY DISEASE CHARACTERISTICS: More than 80% had metastatic disease; tumor types not reported

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

• RCT

• Brief Pain Inventory

Pain and analgesic knowledge increased significantly from baseline in both groups, and pain intensity and interference decreased significantly in both groups from baseline (p < .05). Knowledge improved the most in patients who had not previously used analgesics. Pain intensity declined more in the intervention group.

Education and counseling were associated with improvement in pain scores.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Selective outcomes reporting
• Other limitations/explanation: Possibility of testing bias with repeated measure of the same tool. It is not clear if there was potential for contamination if the study was done in the same inpatient settings. It is stated that pharmacists made recommendations based on patient responses, but it is not stated if pain control regimens were changed during the study or what analgesics patients were receiving, so it is impossible to know if the education intervention was responsible for differences found.

The likely effectiveness of psychoeducation for improving pain control is known; this study supports that evidence in an inpatient setting.

To observe the curative effect of an acupoint application with a Dingqi analgesic patch on moderate-to-severe pain caused by liver cancer

Patients were randomized to a control or a treatment group. Patients with visual analog scale (VAS) scores of 4–6 were given 100 mg sustained-release tramadol daily. Those with VAS scores of 7–10 were given 4.2 mg fentanyl transdermal every three days. The treatment group was given the acupoint patch consisting of a mixture of traditional Chinese herbs on one to two pain points. The control group was given the same size patch without medication. The VAS scores were assessed at intervals throughout the 12 days of treatment.

• N = 40
• AGE = 18–80 years
• MALES, FEMALES: Not available
• KEY DISEASE CHARACTERISTICS: Liver cancer with pain

• SITE: Single site 
• SETTING TYPE: Not specified 
• LOCATION: China

• PHASE OF CARE: Transition phase after active treatment
• APPLICATIONS: Elder care

• Single-blind, randomized, controlled study

• VAS
• Karnofsky Performance Scale

Findings suggest that the Dingqi patch might be helpful in pain management; however, this study provides very limited support for this approach.

• Small sample (less than 100)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Other limitations/explanation: This study shows a decrease in pain over the 12-day period, almost equivocal in the treatment and control group. The patients scored their pain on the VAS scale and were given either controlled-release tramadol or Duragesic^® patches at the start of the study, in addition to the Dingqi patch, or the control patch. Additionally, during the 12 days, if a patient scored a 4–6 on the VAS, they were given a 50 mg tramadol injection; if they scored a 7–10 on the VAS, they were given a 5 mg morphine injection. The report was very limited with no information on patient demographics. Actual data are not reported.

This study does not provide evidence in support of the use of this analgesic patch for pain.

To determine the feasibility, safety, and effects of endoscopic ultrasound (EUS)-guided direct celiac ganglion irradiation with iodine-125 seeds in patients with pain secondary to unresectable pancreatic cancer

Patients were prehydrated and given intravenous ciproflosacin during the procedures and postoperatively for three days. After identification of celiac ganglion, two to four seeds were inserted via the biopsy channel of the endoscope. Computed tomography scans and abdominal radiography were done the day after surgery to ensure correct placement. Postoperative drug therapy was done following World Health Organization guidelines. None of the patients received radiotherapy. Patients were followed weekly until death.

• The study reported on a sample of 23 patients.
• Median patient age was 64 years, with a range of 38–77 years.
• The sample was 61% male and 39% female.
• All patients had unresectable pancreatic cancer.
• Half (50%) of the patients were within two months of diagnosis, and 50% had not had any previous antitumor treatment.

• Single site
• Multiple settings
• China

• Patients were receiving palliative care.
• The study has clinical applicability for late effects and survivorship.

An observational, prospective study design was used.

Pain visual analog scale (VAS)

Average duration of follow-up was 79 weeks (range 43–156 weeks). Patients received morphine sulfate for pain. Baseline VAS mean score was 5.78 (range 4–8), and average morphine sulfate conception was 68.26 (range 40–90). Initial pain score and opioid consumption increased over the first two weeks. By week 3, pain and opioid consumption declined, and by week 7 VAS mean score was 2.91 (range 1–6) and morphine sulfate consumption was 40.45 (range 20–80). These values continued to decline weekly.  By five months, only two patients remained: pain score was 1.5 and opioid consumption with morphine sulfate was 20. None of the patients achieved complete relief of pain. No procedure complications were reported.

The EUS-guided celiac ganglion irradiation with iodine-125 seeds as done here was effective in reducing pain in these patients with pain due to unresectable pancreatic cancer.

• The study has a small sample size, with less than 30 patients.
• The study has risk of bias due to no control group, no blinding, and no random assignment.
• Validity and reliability of measurement is questionable.
• Findings are not generalizable.
• The exact timing and method of VAS scoring is not described.
• Findings are only applicable to patients with unresectable pancreatic cancer.

Control of pain secondary to pancreatic cancer is a challenge, and many of these patients had severe intractable pain. The procedure tested here showed a positive effect for pain control. As such, this procedure may provide another option for pain management in these patients as an adjunct to other pain control approaches. Further well-designed research in this area is warranted, and studies comparing various pain-control methods in this group of patients would be helpful to identify the most beneficial approaches.