The trial had three arms: Group 1 – chemotherapy control, Group 2 – chemotherapy plus midazolam, and Group 3 – chemotherapy plus propofol.

The study reported on a sample of 45 patients with breast cancer (s/p mastectomy, second chemotherapy).

Turkey

A randomized controlled trial design was used.

Clinical Global Impression Scale (CGI) for anxiety

Midazolam and propofol significantly decreased anxiety, with propofol being better.

It is unclear which groups completed the CGI measure.

• FINAL NUMBER STUDIES INCLUDED = 9
• TOTAL PATIENTS INCLUDED IN REVIEW = 788 
• SAMPLE RANGE ACROSS STUDIES = 22–235 patients
• KEY SAMPLE CHARACTERISTICS: Age ranged from 46–60 years with a mean of 55.5 years; 54.2% were female and were receiving treatment; most common treatment was chemotherapy; average months since diagnosis was 8.2 months; most common diagnoses were breast and prostate cancers

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

Supervised multimodal exercise programs resulted in an overall reduction of fatigue in cancer survivors (SMD = –0.23, p = 0.001) with low statistical heterogeneity. Slight evidence of publication bias was noted. Length (weeks of training), frequency (sessions/week), and duration (minutes/session) were linearly associated with overall improvement in CRF (Tau squared = 0.04, p = 0.04). Aerobic exercise, resistance training, and stretching were implemented in seven of the nine studies, and the pooled effect estimate showed significant reductions in CRF (SMD = –0.35, p = 0.01). Two studies used resistance training, and the pooled effect estimate showed no significant reductions in CRF (SMD = –0.17, p = 0.3). Reported adverse events occurred infrequently (n = 7 events, one requiring hospitalization). Most studies were conducted during treatment (chemotherapy) and resulted in significant reductions of CRF (SMD = –0.23, p < 0.0001). No significant reductions in CRF were reported after anticancer treatment (p = 0.1).

Supervised multimodal exercise programs implemented during treatment are supported as an intervention for reducing CRF.

• Considerable statistical heterogeneity in effect estimates existed.
• Risk of bias was evaluated by a single investigator.

Supervised multimodal exercise programs are safe and beneficial for patients receiving anticancer therapy. Referrals to exercise professionals to plan a personalized exercise program for patients with cancer is recommended.

• Randomized, controlled trials
• Participants: Patients with any type of cancer without restriction to a particular stage of diagnosis or treatment
• Intervention: Supervised physical activity interventions (i.e., aerobic, resistance, stretching)
• Outcome measures: Cancer-related fatigue (primary outcome), physical wellbeing, and functional wellbeing
• Comparisons: Supervised physical activity versus conventional care

PHASE OF CARE: Active

The interventions had a mean duration of 17 weeks (SD = 12) with an average of three sessions (SD = 1) per week. The mean session duration was 45 minutes (SD = 29). The interventions included aerobic exercise (i.e., walking, stationary cycling) in all trials, resistance training in six trials (55%), and stretching/flexibility exercises in four trials (36%). Training intensity varied considerably among studies, ranging from 50%–90% of maximum heart rates. All studies reported pre-exercise screening before high intensity physical training. The overall meta-analysis showed that supervised physical activity had a favorable effect on cancer-related fatigue when compared to conventional care. The final analysis of the results revealed that supervised physical activity interventions were effective in the management of cancer-related fatigue for all types of cancer. The favorable effect was no longer significant at the six-month follow-up. However, more participants in the intervention group continued to exercise.

This study provides additional support for exercise in management of cancer-related fatigue during active treatment, in this case supervised activity. It reinforces the role of physiotherapy in the management of cancer-related fatigue.

Publication bias may have been present, but it was not possible to test for it because of the small number of included studies. Heterogeneity was present in most of the meta-analyses. This may be because of the range of sample sizes, the diverse exercise regimens (in terms of length, duration, and intensity) evaluated, and the wide variety in outcome measurement tools used in the included studies

Nurses can continue to recommend exercise as an intervention for cancer-related fatigue. However, additional research is still needed on the type, frequency, intensity, and duration of exercise.

• FINAL NUMBER STUDIES INCLUDED = 9 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,156
• KEY SAMPLE CHARACTERISTICS: Of the trials, 67% were conducted during active treatment. The mean age was 55.2 years, and the studies were mainly of non-Hispanic Caucasians.

PHASE OF CARE: Multiple phases of care

All trials included aerobic training, and six included resistance training. The average duration of training was 21 weeks, and the average sessions per week was 2.5. Supervised aerobic exercise was more effective than usual care in improving fatigue (SMD = –0.51, 95% confidence interval [CI] [–0.81, –0.21]). SMD for resistance training was –0.41 (95% CI [–0.76, –0.05]). No dose response for training intensity was seen. Studies conducted during active treatment showed a significant benefit in reducing fatigue (SMD = –0.66, p < 0.05). In four studies conducted after cancer treatment, the effects of exercise on fatigue were not significant. Exercise improved physical well-being, but no significant effects were observed for social and emotional domains.

Supervised aerobic training during cancer treatment was associated with a significant improvement in fatigue.

• High heterogeneity among the studies
• The analysis was limited to the use of supervised exercise compared to only usual care.
• The number of studies reporting emotional and psychosocial outcomes was small.

Exercise during cancer treatment has been shown to reduce fatigue. This study suggests that the results may be best with aerobic exercise. The optimum intensity and “dosage” of exercise at various time points in cancer treatment remain unclear.

To study the effectiveness of acupuncture and acupressure in reducing chemotherapy-induced nausea

Patients were treated for one cycle of chemotherapy with acupuncture and acupressure at point P6 and for one cycle at a close sham point. Participants were randomized to acupuncture at P6 or at a close nonacupuncture point, and it was delivered by one of two physicians with training and experience in acupuncture. Participants wore acupressure bands for 72 hours at the same points on both arms and could wear them for an additional four days if needed. The bands were covered with a mull bandage to blind the staff. Participants completed diaries for seven days, documenting intensity (on a 0-6 rating scale), frequency, and duration of nausea and vomiting; additional antiemetics taken; and, on day 7, rate the effectiveness of side effects or impairment by acupuncture or acupressure. Patients completed the Morrow Assessment of Nausea and Emesis (MANE). Oncology staff checked that the diaries were completed accurately, standard antiemetics regimens were followed, and if any adverse reactions related to acupuncture occurred.

• The study consisted of 28 patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC).
• Patients were eligible for the study if they
  • Were 18-75 years old.
  • Were scheduled to receive MEC or HEC and standard antiemesis additional medication for rescue predefined for two cycles of chemotherapy.
  • Had a Karnofsky index of 50%.
• Patients were excluded from the study if they had
  • Received chemotherapy within the last three months.
  • Experienced anticipatory nausea and vomiting, cerebral metastasis, chronic ileus or subileus, or lymphedema in arms.
  • Prior knowledge of acupressure points.

The study was conducted by the hematology and gastroenterology departments of a large university hospital in Germany.

This was a randomized, crossover pilot study.

• The MANE, shortened version, was used to measure nausea.
• Patients recorded the Intensity, frequency, and duration of nausea in patient diaries.

• No difference was found between combined acupuncture and acupressure at the P6 point and at the sham point.
• The study was stopped early because of recruitment problems and low incidence of nausea and vomiting in the sham group.
• Half of the participants reported an irradiating feeling, which is a sign of effective acupuncture.

• The sample size was small.
• Incidence of nausea was low in the sham group.
• No acupuncture control group was included.
• No control was included for type of cancer or chemotherapy regimen.
• The sham point may have been too close to P6 or the needle was too deep.

To assess the impact of orally administered prolonged-release (PR) naloxone on the analgesic effectiveness of PR oxycodone and on constipation in patients with severe chronic pain.

The study comprised three phases:

1. Patients entered either a two-week titration or a seven-day run-in period. Patients were individually titrated and stabilized on an oxycodone PR dose of 40, 60, or 80 mg/day.
2. Patients were randomized to four study groups, each comprising a balanced ratio of 40-, 60-, or 80-mg PR oxycodone with placebo or 10- to 40-mg naloxone. Rescue pain medication (up to five 10-mg oxycodone doses per week) was allowed during the maintenance phase.
3. In a two-week open-label phase, patients stopped naloxone therapy and continued PR oxycodone.

• The study reported on a sample of 202 patients aged older than 18 years, with a mean age of 53.8 years.
• The sample comprised 75 men (37.1%) and 127 women (62.9%).
• Only 2.5% of the original 202 screened patients had cancer.
• Most common pain-causing diseases or conditions were back pain (24.3%) and postoperative complications (15.3%).
• Mean duration of pain was 149.3 months.

• Multi-site
• 28 sites in Germany

This was a prospective, placebo-controlled, randomized, double-blind, parallel-group, phase II study.

• Bowel Function Index (BFI)
• Numerical Analog Scale (NAS) for pain assessment

• At week 6, BFI score was statistically significantly different between the 40-mg naloxone and placebo control groups, showing a decrease of severity in bowel dysfunction with naloxone (p = 0.004). 
• At the end of week 8, both 20- and 40-mg naloxone groups had significant differences in BFI scores compared with placebo (p < 0.05).
• No differences existed in mean pain scores between treatment groups at any study time points.
• Titration of participants off of PR oxycodone/naloxone back to single PR oxycodone regimens during the open-label phase resulted in decreased bowel function, and BFI scores returned almost to baseline.
• The incidence of adverse events (AEs), most of which were mild to moderate, was comparable across all treatment groups, although the number of AEs increased along with naloxone dosage.

The study provided evidence that a combination of PR oxycodone/PR naloxone in a 2:1 ratio could enable patients with chronic pain to achieve both adequate pain control and bowel evacuation function.

The study only looked at oxycodone for pain control and did not include many patients with cancer.

An oral combination of PR oxycodone/PR naloxone in a 2:1 ratio seems to improve bowel function without compromising analgesia in patients with chronic pain. Additional study should include patients with cancer and a variety of other opioids.

To evaluate the use of oral naloxone for the management of opiate-associated constipation in patients with cancer.

Patients were observed for six days without intervention. Afterward, oral naloxone was titrated as follows: 3 mg TID (day 1), 6 mg TID (day 2), 9 mg TID (day 3), 12 mg TID (day 4; maximum). Titration was stopped with laxation or increased peristalsis.

• The study reported on a sample of 22 patients.
• The final sample included 17 patients.

Hospital in Germany

This was a controlled study with a control period, but not a control group.

• Himmelsbach Withdrawal Scale was used to monitor possible systemic withdrawal signs such as shivering or piloerection, yawning, perspiration, nausea or vomiting, tremor or restlessness, and lacrimation or rhinorrhea. Each sign was quantified as 0 (none), 1 (mild), 2 (moderate), or 3 (severe).
• Laxation frequency
• Pain intensity on an 11-step numerical rating scale
• Laxatives received
• Ratio of morphine dose to naloxone dose

• Nausea, restlessness, and sweating were the most common side effects.
• Laxation increased in 14 of 17 patients, whereas laxative use decreased in 9 of 17 patients.
• No difference existed in pain rating between study periods.
• Other laxatives used were lactulose, paraffin, raglan, glycerol, castor oil, and sodium picosulfate.
• Naloxone dose was based on opioid-tolerance level rather than morphine dose.

Starting with a low dose of naloxone and titrating up is recommended.

• Only six days were allocated for measurement periods.
• A subjective Likert-type scale from 0 to 3 was used.
• No control group existed for other laxative use (all participants were on at least one).
• Overdosed patients (via medication error) were kept on the study.
• The study did not control for diet, exercise, and fluid intake.
• The p-value was not tested.

Medical information was collected from a computer database. Patients received either DMPA or D- tryptophan -6-leutenizng hormone-releasing hormone agonist (GnRH-a) or no treatment before myelosuppressive chemotherapy.

 

• N = 101 (42 received DMPA, 39 received GnRH-a, 20 remained untreated)
• MEAN AGE = 29.8 years
• OTHER KEY SAMPLE CHARACTERISTICS: 93 had BMT, and eight had non-ablative regimens. Only patients who developed thrombocytopenia less than 25k were included in the study. Patients had confirmed ovarian function. Patients were excluded who were receiving hormonal therapy, including oral contraceptives, immediately prior to therapy.
   

• Retrospective clinical study

• Severe thrombocytopenia = platelets less than 25K
• Number of days of thrombocytopenia
• Number of blood units required
• ANOVA—if ANOVA 0.05 level paired comparisons with Mann-Whitney
• Multiple comparisons with Student-Newman-Keuls
• General bleeding, amount of bleeding, and number of gynecologic visits tested with chi-square
• Nonvaginal bleeding (1 = no bleeding, 2 = mild—mucosal bleeding or skin hemm, 3 = moderate bleeding—bleeding from major organ system, 4 = severe—life threatening)
• Vaginal bleeding (1 = none, 2 = spotting mild, 3 = moderate—daily blood loss comparable to regular menses but requiring intervention because of duration, 4 = significant, requiring intervention)

Four patients were excluded because of gynecologic pathology. Average days of thrombocytopenia was 24.75 +/- 23.6 days. There was no statistical significant difference between groups regarding duration of thrombocytopenia. There was no difference in moderate to severe nonvaginal bleeding. There was no difference in platelet /packed red blood cells and fresh frozen plasma transfusions. Moderate/severe vaginal bleeding occurred in 16.8%—both treatment groups had lower rates of menorrhagia than untreated groups. None of the GnRH-a group had moderate/severe vaginal bleeding (p-0.002). There was a need for urgent gynecologic consult—untreated versus treated (P < 0.0001). Urgent treatment with estrogen was needed in the DMPA group but not the GnRh-a group (P = 0.004).

 
 

To compare the use of medical clowning with the use of local anesthetic cream or the use of no intervention on pain in children undergoing a procedure

The study authors evaluated the use of a trained medical clown with the application of an anesthetic cream or no intervention on the effect on children’s pain and anxiety associated with a procedure. The control group underwent a blood draw/venipuncture without any intervention. The medical clown group had the clown distract and entertain the child from 10 minutes before as well as during and after the procedure. The final group had children given a local anesthetic containing a mixture of lidocaine and prilocaine 50 minutes prior to the blood draw/venipuncture. Duration of crying was measured by an independent observer, pain level was assessed by the child using the visual analog scale (VAS) for pain, and pain and anxiety were also assessed from the parents' perspective using VAS for pain and anxiety during a follow-up phone call.

• N = 100   
• AGE = 2–10 years
• MALES: 53%, FEMALES: 47%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: Unknown

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Carmel Medical Center

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics

• Randomized, controlled trial

• Visual analog score (VAS) for pain ratings by children and parents, similar VAS for anxiety rated by parents
• Observation of duration of crying by an independent trained observer
• Wong-Baker FACES Pain Rating scale used for the children

The duration of the child crying was significantly shorter with the clown group than in the control group (p = 0.01). The duration of crying prior to the procedure was significantly shorter in the clown group compared to the EMLA cream group (p < 0.05) and control group (p < 0.01). The child’s assessment of pain was significantly less in the EMLA group compared to the control group (p = 0.04), but no difference existed between the clown and control groups. The parent’s assessment of the child’s pain was lowest in the clown group (p < 0.05 between all groups). Parent’s assessment of future anxiety was significantly lower in the clown group than the EMLA group or control group (p < 0.05).

The use of the medical clown had a positive effect on parents’ anxiety for future venipuncture as well as anticipatory crying duration and perception of pain in children.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Possible differences in children’s diagnoses and reason for venipuncture

Nurses should be aware of alternative methods such as the use of a medical clown for distracting or controlling children’s pain. Although medicine is shown to have a significant effect on the child’s pain, these methods can assist with both children and parents’ anxiety and management of pain.

To compare the effectiveness of dronabinol alone or in combination with ondansetron versus ondansetron alone for delayed, chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in multiple cancer centers

• The study took place over five days.
• Participants were randomized to four treatment groups: dronabinol alone, ondansetron alone, combination with both drugs, and placebo. 
• Standard pretreatment medications, fixed doses on day 2, and flexible doses days 3-5 were administered.
• Participants were assessed based on patient telephone diary entries. Each morning, patients reported symptoms from the previous day via the Interactive Voice Response System.

• The study consisted of 64 participants, aged 18 years or older, with a malignancy that did not involve bone marrow.
• Participants were undergoing chemotherapy regimens and had performance statuses of 0–2 at screening. They could be receiving concurrent radiation except to the abdomen and changing regimens with last antiemetics seven days prior to study enrollment.
• For women, a negative pregnancy test at baseline was required.
• Diagnoses involved primary malignancy of the brain, spinal cord, or nervous system; brain metastases; severe brain trauma or surgery; leukemias; or lymphomas.
• Patients who had used marijuana within 30 days or antiemetics within 7 days were excluded from the study.

The study was conducted at multiple cancer centers.

This was a randomized, double-blind, placebo-controlled, parallel-group study.

The following measurement instruments were used.

• Visual analog scale (VAS)
• Total response
• Intensity of nausea
• Eastern Cooperative Oncology Group (ECOG) performance status
• McCorkle Symptom Distress Scale

Difficulties in enrollment led to early termination of this study.

• The efficacy of dronabinol alone was comparable with ondansetron for the treatment of delayed CINV in patients with cancer receiving HEC or MEC.
• Combination therapy with dronabinol and ondansetron was not more effective than either agent alone.

• Patients had difficulties with potential for randomization to placebo when receiving HEC or MEC.
• Early discontinuation of the study reduced the number of participants enrolled in each treatment group.
• The population was heterogeneous.
• No control chemotherapy treatment was used.
• The majority of patients had breast or lung cancer.