Databases searched were MEDLINE (1966–2005), EMBASE (1974–2005), Cochrane Central Register of Controlled Trials (issue 2, 2005), and specialized registers of the Cochrane Cancer Network and the Cochrane Pain, Palliative and Supportive Care Group. Also searched were metaRegister of Controlled Trials, U.S. National Institutes of Health register, register of the Center for Clinical Trials and Evidence-Based Healthcare, and register of the European Organization for Research and Treatment of Cancer.

Registers of trials in progress also were assessed.

Studies were included in the review if they

• Reported on calcitonin plus a rescue medication versus placebo plus a rescue medication
• Used any comparison between different models and intervention doses of interest
• Included use of steroids or analgesic radiotherapy if administration was equal in each treatment arm.

Studies where bisphosphonates were administered before patients were randomized to different treatment arms and studies where the efficacy of calcitonin in treating pain was measured over a short period (less than four weeks) were excluded.

The review included two randomized, double-blind clinical trials of patients with metastatic bone pain for a total of 90 patients. The first study compared calcitonin (100 IU administered subcutaneously each day for 28 days) versus placebo administered to a group of 40 women with breast cancer and pain from bone metastasis. The second study compared calcitonin (100 IU administered subcutaneously each day for three months) versus placebo in 50 women with breast cancer and painful bone metastases.

Of the two studies selected (90 patients), all patients had metastatic bone pain caused by any primary tumor, diagnosed by computed tomography, bone gammagraphy, nuclear magnetic resonance, or other radiographic process.

The limited available evidence does not support the use of calcitonin to control pain from bone metastases.

Calcitonin has been assessed in studies with small sample sizes and too short-term evaluations.

More double-blind, parallel clinical trials using long-term evaluations are needed.

STUDY PURPOSE: To evaluate the effectiveness of healthcare interventions targeting pain in patients with cancer

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed, CINAHL, PsycINFO, DARE, and Cochrane Collaboration; reference lists were used to identify additional studies.

KEYWORDS: Search terms and strategy specifics are in an online appendix to this article.

INCLUSION CRITERIA: Random or nonrandom trials with a control group. Patient-centered and institutional change interventions were included in the definition of healthcare interventions. Pain was included as an outcome.

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED = 1,3014

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: GRADE system of quality evaluation; risk of bias was high in seven studies and moderate in another seven studies.

• FINAL NUMBER STUDIES INCLUDED = 19 
• TOTAL PATIENTS INCLUDED IN REVIEW = 97
• KEY SAMPLE CHARACTERISTICS: Mixed tumor types; median follow-up was 8 weeks (range was 2–24 weeks); all had advanced cancer.

APPLICATIONS: Palliative care

Of the studies, 89% examined patient educational activities. Two focused on provider-level interventions. Fifty-five percent of studies (11 studies) that measured knowledge and barriers found significant improvement in barriers to pain management. Five studies measured pain knowledge–two of these showed improvement. Forty-seven percent of the 19 studies showed significant improvement in pain outcomes compared to the control group. Findings varied by the type of intervention used, and results suggest that the use of multiple educational modalities may be more effective. The number of patient encounters in studies varied widely.

Psychoeducational interventions significantly can reduce barriers to pain management, improve pain knowledge, and improve pain outcomes.

• Many studies had small sample sizes and moderate to high risk of bias. 
• The samples had little ethnic diversity. 
• Although most used the Brief Pain Inventory, studies used different components of the tool and individual subscales only.

Psychoeducational interventions can reduce patient barriers to pain management, improve relevant knowledge, and have a positive impact on pain. Multimodal interventions combining various educational media and follow-up appear to be more effective than alternatives. Data are limited to show effects of institutional, provider-focused interventions, but results in this area are promising. A combination of provider- and patient-focused interventions should be evaluated.

To use a bundle approach to reduce central line–associated bloodstream infections (CLABSI) in patients with hematologic malignancies and neutropenia with long-term central venous catheters (CVC)

Between 2010 and 2012, a bundle of interventions was introduced and outcomes were compared with the results from six months prior to the intervention. Interventions were the use of a different catheter (a neutral pressure mechanical valve connector versus a positive pressure mechanical valve connector), changing needless connectors twice weekly instead of weekly, and the replacement of a chlorhexidine solution to clean needless connectors rather than a solution with 70% alcohol. If blood cultures were obtained, patients were put on broad spectrum antibiotics. All patients were receiving prophylactic co-trimoxazole, itraconazole, and environmental neutropenic precautions.

• N = 116   
• AGE = older than 18 years
• MALES: Not provided  
• FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: Patients with acute leukemia, multiple myeloma, or non-Hodgkin lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: All had tunneled catheters

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Portugal

• PHASE OF CARE: Active antitumor treatment

• Prospective with historical cohort comparison

Blood cultures were obtained for the presence of a fever for more than one hour or other signs of infection from peripheral veins and CVC lines.

With the intervention, a 71% reduction in both CLABSIs (risk ratio [RR] = 0.29, p < 0.014) and overall bloodstream infections (RR = 0.28, p < 0.001) occurred. The reduction of gram-positive bacteria was most pronounced.

The institutional protocol changes related to catheter selection and IV access system care were associated with a reduction in CLABSIs.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Limited sample description.
• Outcomes measured at 72 hours only
• No information was provided regarding other aspects of care or techniques used in insertion.

The changes implemented here were associated with the reduced incidence of CLABSIs within 72 hours. The authors suggested that changing from a positive pressure valve catheter to a neutral pressure type catheter may have been most relevant, as positive pressure valves tend to develop a biofilm and cannot be cleaned well with routine flushing.

STUDY PURPOSE: To assess safety and efficacy of interventions used to prevent blood loss during treatment of cervical intraepithelial neoplasia (CIN)

TYPE OF STUDY: Meta-analysis and systematic review

PHASE OF CARE: Active antitumor treatment

• Vasopressin versus placebo: One trial showed significant reduction in blood loss (MD -100.9, p < 0.00001). One trial examined selective bleeding and showed a significant reduction with vasopressin (RR = 0.4, p < 0.0001)
• Tranexamic acid (TA) versus placebo: One trial showed reduction in postoperative blood loss with TA (MD -55.6, p < 0.0001). Analysis of two trials showed no meaningful difference in the risk of primary hemorrhage (RR = 1.24), and across four trials, there was significantly reduced risk of secondary hemorrhage with TA (RR = 0.23, p = 0.00017).
• Vaginal pack with Monsel’s solution: Vaginal packs were associated with significant reduction in perioperative blood loss and decreased risk of dysmennorhea compared with hemostatic sutures (p < 0.05).

Vasopressin, TA, and vaginal packs with Monsel’s solution appear to be helpful in reducing blood loss in women with CIN undergoing surgical procedures. Findings are limited because few studies exist comparing specific interventions.

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

This review contains limited evidence; however, findings suggest that use of vasopressin, TA, and vaginal packs with Monsel’s solution may be helpful to reduce various types of procedure-related bleeding in women with CIN.

To evaluate the effects of a six-week yoga intervention on caregivers’ overall quality of life and psychological distress

Caregivers participated in a particular type of yoga called vinyasa yoga (VY) for 150 minutes per week, which was conducted in two 75-minute sessions for six weeks. Each VY session included breathing exercises, meditation, poses, and a particular subtype of VY called savasana that promotes relaxation and relieves stress.

• N = 12
• AGE = 18–65 years
• MALES: 8%, FEMALES: 92%
• KEY DISEASE CHARACTERISTICS: Participants were the informal, unpaid caregivers of patients with cancer. No information is provided about the type of cancer. 
• OTHER KEY SAMPLE CHARACTERISTICS: Caregivers who reported a level of distress that was disrupting their lives based on the National Comprehensive Cancer Center Distress Thermometer were included in the study. 

• SITE: Single site  
• SETTING TYPE: Other  
• LOCATION: Dalhousie University public recreational facility, Canada

• PHASE OF CARE: Multiple phases of care

• A single-group, pre- and post-test pilot study

• Profile of Mood States (POMS)
• TMD = total mood disturbance or overall psychological distress
• SF-36, version 2 to measure quality of life

The overall attendance rate was 65%. Participants had a mean baseline distress score of 6.5 out of 10. A significant difference was seen in TMD scores from baseline to post-intervention (p = 0.002). Although no significant difference was seen in the physical component score of SF-36 from baseline to post-intervention, a significant difference was seen in the mental component scores of SF-36 from baseline to post-intervention (p = 0.018). The effect in the intended outcome for TMD scores and MCS was large.

Cancer caregivers may benefit mentally with reduction in psychological distress from VY.

• Small sample (less than 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Risk of bias(sample characteristics)
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: Although this study shows some positive findings, including reduction in psychological distress and improvement in the mental component of quality of life, small sample size and the absence of a control group reduce the strength of this study. Also, the majority of the participants were women, which reduces the generalization of the findings to both genders. Details regarding who conducted the yoga teaching and whether they are trained in yoga are not provided in the study.

VY seems to be a cost-effective approach to improve the quality of life and psychological distress in cancer caregivers. Nurses can encourage caregivers to participate in VY programs. RCTs with larger sample size are needed to find the true effect of yoga on cancer caregivers in terms of reducing psychological distress and improving quality of life.

To describe the effect of denosumab on pain and analgesic use in patients with giant cell tumor of bone (GCTB)

Patients were split into two groups, cohort 1, which contained patients with unresectable disease or multiple lesions, and cohort 2, which contained patients with resectable disease but for whom surgery was associated with high morbidity. Patients received denosumab every four weeks with additional doses on days 8 and 15. Pain was assessed with the Brief Pain Inventory Short Form at baseline and each visit for the first six months and every three months thereafter.

• N = 271  
• AVERAGE AGE: 33.5 years
• MALES: 41%, FEMALES: 59%
• KEY DISEASE CHARACTERISTICS: Patients had either unresectable disease or had disease associated with high morbidity; ≥ 12 years old with active histologically confirmed GCTB

• SITE: Multi-site  
• SETTING TYPE: Not specified    
• LOCATION: Multiple international centers

• PHASE OF CARE: Mutliple phases of care
• APPLICATIONS: Elder care and palliative care 

• Phase II, prospective clinical trial

• The Brief Pain Inventory Short Form (BPI-SF) was used to evaluate pain and minimally important differences.
• The Analgesic Quantification Algorithm (AQA) was used to evaluate analgesic use at each visit.

Denosumab is a reasonable treatment choice for pain relief in patients with GCTB with unresectable disease, disease with multiple lesions, or for patients in whom resection would be associated with high morbidity. This treatment would reduce radiotherapy-related risks and provide a medical option for treating patients in who  surgical intervention (the treatment of choice) is not a option or is presented as a high-risk option.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Denosumab is an easy drug to administer that has few side effects. Education on the drug and its administration would be required to effectively treat patients limited to this option. Nurses could help advocate for patients with unresectable disease or disease associated with high morbidity with surgery. This could be an alternative to radiation if patients are unable to receive radiation or are concerned about the low but present risk of secondary tumors from radiation treatment.

STUDY PURPOSE: To assess the benefits and harms of pharmacologic interventions for treating patients with leukemia experiencing disseminated intravascular coagulation (DIC) to update a prior systematic review

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 4 studies 
• TOTAL PATIENTS INCLUDED IN REVIEW = 388
• SAMPLE RANGE ACROSS STUDIES: 10–132

PHASE OF CARE: Not specified or not applicable

Interventions included human activated protein C versus heparin, recombinant human soluble thrombomodulin versus heparin, tanexamic acid versus placebo, and dermatan sulfate versus heparin. Only one study was found for each intervention. No significant differences in bleeding with protein C or dermatan sulfate existed. Recombinant human soluble thrombomodulin was associated with improvement in bleeding symptoms compared to heparin, and lower scoring of hemorrhagic problems with tranexamic acid compared to placebo.

Insufficient high quality evidence exists to fully evaluate these interventions.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Low sample sizes
• Some studies included patients with DIC from other causes, and the findings were not reported separately for patients with leukemia, further reducing the relevant samples for consideration.

Extremely limited evidence regarding the effects of pharmacologic interventions for the management of DIC and associated bleeding exists compared to usual practice using heparin.

To determine the effectiveness of octreotide in reducing treatment-related diarrhea during radiation therapy to the pelvis

Patients were randomized to receive octreotide acetate or placebo. Patients in the treatment group were given 100 µg subcutaneous octreotide acetate on day 1 followed by 20 mg intramuscular octreotide acetate on days 2 and 29. Patients in the control group received placebo by the same routes on the same days.

• The study reported on 125 patients.
• Patients had histologic proof of cancer in the pelvis without distant metastases and were receiving radiation therapy, either as definitive treatment or adjuvantly.                           

This was a multisite, collaborative trial of North Central Cancer Treatment Group.

Patients were undergoing the active treatment phase of care.

This was a double-blinded, randomized control trial.

A Bowel Function Questionnaire and a Uniscale Quality of Life (QOL) measure were used.

No statistically significant differences were found between groups. Octreotide did not reduce the severity or incidence of diarrhea during pelvic radiation therapy. Abdominal cramps were worse in patients on the octreotide arm, but the difference was not statistically significant (p = 0.053). Patients receiving octreotide experienced significantly more problems with nocturnal bowel movements (70% versus 45%, p = 0.004), clustering (90% versus 69%, p = 0.004), and blood with bowel movements (57% versus 35%, p = 0.01).

Octreotide did not result in improvement in diarrhea in this population and was associated with more problems. Octreotide did not have an effect on the severity or incidence of diarrhea during pelvic radiation therapy. Some gastroinstestinal (GI) symptoms were worse in patients receiving octreotide compared to placebo.

• The subjects in the treatment groups were different. More patients in the control group had histories of rectal surgery or primary rectal cancer.
• Not all patients completed the day 29 dose of study medication. Only 49 (79%) of 62 of patients in the placebo arm and 43 (69%) of 62 of patients in the octreotide arm received a second dose.
• No intention-to-treat analysis was conducted.

More clinical research is needed to evaluate the effective prevention of diarrhea during pelvic radiation therapy. Long-acting octreotide (LAO) should not be used outside of a controlled clinical trial setting.

Patients receiving pelvic external beam radiation therapy were randomly assigned to receive sulcrafate (2 gm four times per day) or placebo.

The study reported on 123 evaluable patients. The treatment group consisted of 62 patients, and the placebo group consisted of 61 patients. The two groups were balanced in terms of factors such as diagnosis, functional status, radiation dosage, and tumor status. 

This was a double-blind, randomized controlled trial.

• Patients reported the number bowel movements, use of protective clothing, and symptoms of cramping, blood, nocturnal bowel movements, and fecal incontinence weekly via a questionnaire.
• Physicians assessed diarrhea, tenesmus, cramping, bleeding, nausea, and constipation using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

More patients in the treatment group reported fecal incontinence and a need for protective clothing than in the control group (34% versus 16%, p = 0.04). Physician-reported severity of nausea was worse in the treatment group compared to the control group (p = 0.3), although this was not a specific study endpoint.

Sulcrafate did not decrease pelvic radiation therapy-related bowel toxicity by any of the endpoints measured and seems to have aggravated some gastrointestinal symptoms.

Although the patient questionnaire approximated the physician scale, provider assessments of subjective data such as cramping and straining can be unreliable if not obtained directly from the subject.

To identify if the cool pad pillow topper (CPPT) decreases sleep disturbance, minimizing the effects of hot flashes. The CPPT is a commercial product promoted to improve quality of sleep disrupted by hot flashes.

The intervention arm of pre- and postmenopausal women received during four weeks standard care consisting in booklets with advice on exercise, physical activity, diet, and the reduction of caffeine and alcohol plus the CPPT. The CPPT is an approved commercial product that removes heat from the body and can be placed on top, outside, or inside the pillowcase.

• N = 75  
• MEAN AGE: 49.5 years (intervention group mean = 51 years, and control group mean = 51.2 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer in endocrine therapy, pre- or postmenopausal, night hot flashes
• OTHER KEY SAMPLE CHARACTERISTICS: Insomnia symptoms, anxiety, depression, exercise, alcohol intake, smoking status

• SITE: Not stated/unknown    
• SETTING TYPE: Outpatient    
• LOCATION: The Beatson West of Scotland Cancer Centre, Glasgow

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

• Randomized phase II clinical trial, control with routine information and intervention group information plus the CPPT

The instruments for the intervention group were the sleep diaries to evaluate amount of time asleep and changes in sleep disturbance. The number of hot flashes and the severity at night were evaluated with the hot flash score (HFS), both completed daily for four weeks from the point of randomization; they also record number of alcohol units consumed, if any sleeping pills were taken, and the frequency nightwear changed. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and Hospital Anxiety and Depression Scale (HADS) were used at two points—at randomization and at the end of the study.

CPPT is effective as a self-management strategy to reduce sleep disturbance and the severity/frequency of hot flashes. CPPT did not impact quality of life (QOL) or anxiety but reduction in depression was observed. The CPPT appears to be an effective intervention in conjunction with current standard care.

• Small sample (less than 100)
• Risk of bias (no blinding)
• No main limitations are founded in the well-designed study

Nurses could recommend the use of the CPPT as no risk or harm is expected and it helps control hot flashes and sleep disturbances associated with endocrine therapies. This is a pilot only; would recommend additional research to note if results are reproducible.